Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
NeuroMolecular Medicine
Published in: NeuroMolecular Medicine 2/2010

01-06-2010 | Review Paper

Role of Cytokines as Mediators and Regulators of Microglial Activity in Inflammatory Demyelination of the CNS

Authors: Tobias D. Merson, Michele D. Binder, Trevor J. Kilpatrick

Published in: NeuroMolecular Medicine | Issue 2/2010

Login to get access

Abstract

As the resident innate immune cells of the central nervous system (CNS), microglia fulfil a critical role in maintaining tissue homeostasis and in directing and eliciting molecular responses to CNS damage. The human disease Multiple Sclerosis and animal models of inflammatory demyelination are characterized by a complex interplay between degenerative and regenerative processes, many of which are regulated and mediated by microglia. Cellular communication between microglia and other neural and immune cells is controlled to a large extent by the activity of cytokines. Here we review the role of cytokines as mediators and regulators of microglial activity in inflammatory demyelination, highlighting their importance in potentiating cell damage, promoting neuroprotection and enhancing cellular repair in a context-dependent manner.
Literature
Abbas, A. K., Murphy, K. M., & Sher, A. (1996). Functional diversity of helper T lymphocytes. Nature, 383, 787–793.PubMedCrossRef
Adams, R. A., Bauer, J., Flick, M. J., Sikorski, S. L., Nuriel, T., Lassmann, H., et al. (2007). The fibrin-derived gamma377–395 peptide inhibits microglia activation and suppresses relapsing paralysis in central nervous system autoimmune disease. Journal of Experimental Medicine, 204, 571–582.PubMedCrossRef
Adams, D. H., Hathaway, M., Shaw, J., Burnett, D., Elias, E., & Strain, A. J. (1991). Transforming growth factor-beta induces human T lymphocyte migration in vitro. Journal of Immunology, 147, 609–612.
Aggarwal, S., Ghilardi, N., Xie, M. H., de Sauvage, F. J., & Gurney, A. L. (2003). Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17. Journal of Biological Chemistry, 278, 1910–1914.PubMedCrossRef
Akassoglou, K., Bauer, J., Kassiotis, G., Pasparakis, M., Lassmann, H., Kollias, G., et al. (1998). Oligodendrocyte apoptosis and primary demyelination induced by local TNF/p55TNF receptor signaling in the central nervous system of transgenic mice: Models for multiple sclerosis with primary oligodendrogliopathy. American Journal of Pathology, 153, 801–813.PubMed
Akira, S. (2003). Toll-like receptor signaling. Journal of Biological Chemistry, 278, 38105–38108.PubMedCrossRef
Aktas, O., Prozorovski, T., & Zipp, F. (2006). Death ligands and autoimmune demyelination. Neuroscientist, 12, 305–316.PubMedCrossRef
Albrecht, P. J., Dahl, J. P., Stoltzfus, O. K., Levenson, R., & Levison, S. W. (2002). Ciliary neurotrophic factor activates spinal cord astrocytes, stimulating their production and release of fibroblast growth factor-2, to increase motor neuron survival. Experimental Neurology, 173, 46–62.PubMedCrossRef
Allan, S. M., Tyrrell, P. J., & Rothwell, N. J. (2005). Interleukin-1 and neuronal injury. Nature Reviews Immunology, 5, 629–640.PubMedCrossRef
Allione, A., Bernabei, P., Bosticardo, M., Ariotti, S., Forni, G., & Novelli, F. (1999). Nitric oxide suppresses human T lymphocyte proliferation through IFN-gamma-dependent and IFN-gamma-independent induction of apoptosis. Journal of Immunology, 163, 4182–4191.
Aloisi, F., Penna, G., Cerase, J., Menendez Iglesias, B., & Adorini, L. (1997). IL-12 production by central nervous system microglia is inhibited by astrocytes. Journal of Immunology, 159, 1604–1612.
Aloisi, F., Ria, F., & Adorini, L. (2000). Regulation of T-cell responses by CNS antigen-presenting cells: Different roles for microglia and astrocytes. Immunology Today, 21, 141–147.PubMedCrossRef
Andrews, T., Zhang, P., & Bhat, N. R. (1998). TNFalpha potentiates IFNgamma-induced cell death in oligodendrocyte progenitors. Journal of Neuroscience Research, 54, 574–583.PubMedCrossRef
Araujo, D. M., & Cotman, C. W. (1992). Basic FGF in astroglial, microglial, and neuronal cultures: Characterization of binding sites and modulation of release by lymphokines and trophic factors. Journal of Neuroscience, 12, 1668–1678.PubMed
Arimoto, T., Choi, D. Y., Lu, X., Liu, M., Nguyen, X. V., Zheng, N., et al. (2006). Interleukin-10 protects against inflammation-mediated degeneration of dopaminergic neurons in substantia nigra. Neurobiology of Aging, 28, 894–906.CrossRef
Arnett, H. A., Hellendall, R. P., Matsushima, G. K., Suzuki, K., Laubach, V. E., Sherman, P., et al. (2002). The protective role of nitric oxide in a neurotoxicant-induced demyelinating model. Journal of Immunology, 168, 427–433.
Arnett, H. A., Mason, J., Marino, M., Suzuki, K., Matsushima, G. K., & Ting, J. P. (2001). TNF alpha promotes proliferation of oligodendrocyte progenitors and remyelination. Nature Neuroscience, 4, 1116–1122.PubMedCrossRef
Arnett, H. A., Wang, Y., Matsushima, G. K., Suzuki, K., & Ting, J. P. (2003). Functional genomic analysis of remyelination reveals importance of inflammation in oligodendrocyte regeneration. Journal of Neuroscience, 23, 9824–9832.PubMed
Austin, J. W., & Fehlings, M. G. (2008). Molecular mechanisms of Fas-mediated cell death in oligodendrocytes. Journal of Neurotrauma, 25, 411–426.PubMedCrossRef
Back, S., Tuohy, T., Chen, H., Wallingford, N., Craig, A., Struve, J., et al. (2005). Hyaluronan accumulates in demyelinated lesions and inhibits oligodendrocyte progenitor maturation. Nature Medicine, 11, 966–972.PubMed
Baerwald, K. D., & Popko, B. (1998). Developing and mature oligodendrocytes respond differently to the immune cytokine interferon-gamma. Journal of Neuroscience Research, 52, 230–239.PubMedCrossRef
Bai, X. F., Shi, F. D., Xiao, B. G., Li, H. L., van der Meide, P. H., & Link, H. (1997). Nasal administration of myelin basic protein prevents relapsing experimental autoimmune encephalomyelitis in DA rats by activating regulatory cells expressing IL-4 and TGF-beta mRNA. Journal of Neuroimmunology, 80, 65–75.PubMedCrossRef
Bandtlow, C. E., Meyer, M., Lindholm, D., Spranger, M., Heumann, R., & Thoenen, H. (1990). Regional and cellular codistribution of interleukin 1 beta and nerve growth factor mRNA in the adult rat brain: Possible relationship to the regulation of nerve growth factor synthesis. Journal of Cell Biology, 111, 1701–1711.PubMedCrossRef
Barbara, J. A., Smith, W. B., Gamble, J. R., Van Ostade, X., Vandenabeele, P., Tavernier, J., et al. (1994). Dissociation of TNF-alpha cytotoxic and proinflammatory activities by p55 receptor- and p75 receptor-selective TNF-alpha mutants. EMBO Journal, 13, 843–850.PubMed
Barnett, M. H., Henderson, A. P., & Prineas, J. W. (2006). The macrophage in MS: Just a scavenger after all? Pathology and pathogenesis of the acute MS lesion. Multiple Sclerosis, 12, 121–132.PubMedCrossRef
Barnett, M. H., & Prineas, J. W. (2004). Relapsing and remitting multiple sclerosis: Pathology of the newly forming lesion. Annals of Neurology, 55, 458–468.PubMedCrossRef
Barres, B. A., Schmid, R., Sendnter, M., & Raff, M. C. (1993). Multiple extracellular signals are required for long-term oligodendrocyte survival. Development, 118, 283–295.PubMed
Basu, A., Krady, J. K., O’Malley, M., Styren, S. D., DeKosky, S. T., & Levison, S. W. (2002). The type 1 interleukin-1 receptor is essential for the efficient activation of microglia and the induction of multiple proinflammatory mediators in response to brain injury. Journal of Neuroscience, 22, 6071–6082.PubMed
Batten, M., Li, J., Yi, S., Kljavin, N. M., Danilenko, D. M., Lucas, S., et al. (2006). Interleukin 27 limits autoimmune encephalomyelitis by suppressing the development of interleukin 17-producing T cells. Nature Immunology, 7, 929–936.PubMedCrossRef
Bauer, J., Berkenbosch, F., Van Dam, A. M., & Dijkstra, C. D. (1993). Demonstration of interleukin-1 beta in Lewis rat brain during experimental allergic encephalomyelitis by immunocytochemistry at the light and ultrastructural level. Journal of Neuroimmunology, 48, 13–21.PubMedCrossRef
Baxter, A. G. (2007). The origin and application of experimental autoimmune encephalomyelitis. Nature Reviews Immunology, 7, 904–912.PubMedCrossRef
Becher, B., Dodelet, V., Fedorowicz, V., & Antel, J. P. (1996). Soluble tumor necrosis factor receptor inhibits interleukin 12 production by stimulated human adult microglial cells in vitro. Journal of Clinical Investigation, 98, 1539–1543.PubMedCrossRef
Becher, B., Durell, B. G., & Noelle, R. J. (2003). IL-23 produced by CNS-resident cells controls T cell encephalitogenicity during the effector phase of experimental autoimmune encephalomyelitis. Journal of Clinical Investigation, 112, 1186–1191.PubMed
Becher, B., Prat, A., & Antel, J. P. (2000). Brain-immune connection: Immuno-regulatory properties of CNS-resident cells. Glia, 29, 293–304.PubMedCrossRef
Beck, J., Rondot, P., Catinot, L., Falcoff, E., Kirchner, H., & Wietzerbin, J. (1988). Increased production of interferon gamma and tumor necrosis factor precedes clinical manifestation in multiple sclerosis: Do cytokines trigger off exacerbations? Acta Neurologica Scandinavica, 78, 318–323.PubMedCrossRef
Begolka, W. S., Vanderlugt, C. L., Rahbe, S. M., & Miller, S. D. (1998). Differential expression of inflammatory cytokines parallels progression of central nervous system pathology in two clinically distinct models of multiple sclerosis. Journal of Immunology, 161, 4437–4446.
Benveniste, E. N. (1998). Cytokine actions in the central nervous system. Cytokine and Growth Factor Reviews, 9, 259–275.PubMedCrossRef
Bettelli, E., Carrier, Y., Gao, W., Korn, T., Strom, T. B., Oukka, M., et al. (2006). Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature, 441, 235–238.PubMedCrossRef
Bettelli, E., Das, M. P., Howard, E. D., Weiner, H. L., Sobel, R. A., & Kuchroo, V. K. (1998). IL-10 is critical in the regulation of autoimmune encephalomyelitis as demonstrated by studies of IL-10- and IL-4-deficient and transgenic mice. Journal of Immunology, 161, 3299–3306.
Bezbradica, J. S., & Medzhitov, R. (2009). Integration of cytokine and heterologous receptor signaling pathways. Nature Immunology, 10, 333–339.PubMedCrossRef
Binder, M., Cate, H., Prieto, A., Kemper, D., Butzkueven, H., Gresle, M., et al. (2008). Gas6 Deficiency Increases Oligodendrocyte Loss and Microglial Activation in Response to Cuprizone-Induced Demyelination. Journal of Neuroscience, 28, 5195–5206.PubMedCrossRef
Bjartmar, C., Kidd, G., Mork, S., Rudick, R., & Trapp, B. D. (2000). Neurological disability correlates with spinal cord axonal loss and reduced N-acetyl aspartate in chronic multiple sclerosis patients. Annals of Neurology, 48, 893–901.PubMedCrossRef
Blakemore, W. F. (1973). Demyelination of the superior cerebellar peduncle in the mouse induced by cuprizone. Journal of the Neurological Sciences, 20, 63–72.PubMedCrossRef
Blakemore, W. F. (1982). Ethidium bromide induced demyelination in the spinal cord of the cat. Neuropathology and Applied Neurobiology, 8, 365–375.PubMedCrossRef
Blakemore, W. F., & Patterson, R. C. (1978). Suppression of remyelination in the CNS by X-irradiation. Acta Neuropathologica, 42, 105–113.PubMedCrossRef
Bo, L., Mork, S., Kong, P. A., Nyland, H., Pardo, C. A., & Trapp, B. D. (1994). Detection of MHC class II-antigens on macrophages and microglia, but not on astrocytes and endothelia in active multiple sclerosis lesions. Journal of Neuroimmunology, 51, 135–146.PubMedCrossRef
Brahmachari, S., & Pahan, K. (2009). Suppression of regulatory T cells by IL-12p40 homodimer via nitric oxide. Journal of Immunology, 183, 2045–2058.CrossRef
Brogi, A., Strazza, M., Melli, M., & Costantino-Ceccarini, E. (1997). Induction of intracellular ceramide by interleukin-1 beta in oligodendrocytes. Journal of Cellular Biochemistry, 66, 532–541.PubMedCrossRef
Brok, H. P., van Meurs, M., Blezer, E., Schantz, A., Peritt, D., Treacy, G., et al. (2002). Prevention of experimental autoimmune encephalomyelitis in common marmosets using an anti-IL-12p40 monoclonal antibody. Journal of Immunology, 169, 6554–6563.
Bruck, W., Porada, P., Poser, S., Rieckmann, P., Hanefeld, F., Kretzschmar, H. A., et al. (1995). Monocyte/macrophage differentiation in early multiple sclerosis lesions. Annals of Neurology, 38, 788–796.PubMedCrossRef
Butovsky, O., Ziv, Y., Schwartz, A., Landa, G., Talpalar, A. E., Pluchino, S., et al. (2006). Microglia activated by IL-4 or IFN-gamma differentially induce neurogenesis and oligodendrogenesis from adult stem/progenitor cells. Molecular and Cellular Neurosciences, 31, 149–160.PubMedCrossRef
Butti, E., Bergami, A., Recchia, A., Brambilla, E., Del Carro, U., Amadio, S., et al. (2008). IL4 gene delivery to the CNS recruits regulatory T cells and induces clinical recovery in mouse models of multiple sclerosis. Gene Therapy, 15, 504–515.PubMedCrossRef
Butzkueven, H., Emery, B., Cipriani, T., Marriott, M. P., & Kilpatrick, T. J. (2006). Endogenous leukemia inhibitory factor production limits autoimmune demyelination and oligodendrocyte loss. Glia, 53, 696–703.PubMedCrossRef
Butzkueven, H., Zhang, J. G., Soilu-Hanninen, M., Hochrein, H., Chionh, F., Shipham, K. A., et al. (2002). LIF receptor signaling limits immune-mediated demyelination by enhancing oligodendrocyte survival. Nature Medicine, 8, 613–619.PubMedCrossRef
Calabresi, P. A., Fields, N. S., Maloni, H. W., Hanham, A., Carlino, J., Moore, J., et al. (1998). Phase 1 trial of transforming growth factor beta 2 in chronic progressive MS. Neurology, 51, 289–292.PubMed
Carpentier, P. A., Duncan, D. S., & Miller, S. D. (2008). Glial toll-like receptor signaling in central nervous system infection and autoimmunity. Brain, Behavior, and Immunity, 22, 140–147.PubMedCrossRef
Carrier, Y., Yuan, J., Kuchroo, V. K., & Weiner, H. L. (2007). Th3 cells in peripheral tolerance. I. Induction of Foxp3-positive regulatory T cells by Th3 cells derived from TGF-beta T cell-transgenic mice. Journal of Immunology, 178, 179–185.
Casaccia-Bonnefil, P., Aibel, L., & Chao, M. V. (1996). Central glial and neuronal populations display differential sensitivity to ceramide-dependent cell death. Journal of Neuroscience Research, 43, 382–389.PubMedCrossRef
Chabot, S., & Yong, V. W. (2000). Interferon beta-1b increases interleukin-10 in a model of T cell-microglia interaction: Relevance to MS. Neurology, 55, 1497–1505.PubMed
Chakraborty, G., Ziemba, S., Drivas, A., & Ledeen, R. W. (1997). Myelin contains neutral sphingomyelinase activity that is stimulated by tumor necrosis factor-alpha. Journal of Neuroscience Research, 50, 466–476.PubMedCrossRef
Chan, A., Magnus, T., & Gold, R. (2001). Phagocytosis of apoptotic inflammatory cells by microglia and modulation by different cytokines: Mechanism for removal of apoptotic cells in the inflamed nervous system. Glia, 33, 87–95.PubMedCrossRef
Chan, A., Seguin, R., Magnus, T., Papadimitriou, C., Toyka, K. V., Antel, J. P., et al. (2003). Phagocytosis of apoptotic inflammatory cells by microglia and its therapeutic implications: Termination of CNS autoimmune inflammation and modulation by interferon-beta. Glia, 43, 231–242.PubMedCrossRef
Chao, C. C., Molitor, T. W., & Hu, S. (1993). Neuroprotective role of IL-4 against activated microglia. Journal of Immunology, 151, 1473–1481.
Chari, D., Zhao, C., Kotter, M. R., Blakemore, W., & Franklin, R. J. (2006). Corticosteroids delay remyelination of experimental demyelination in the rodent central nervous system. Journal of Neuroscience Research, 83, 594–605.PubMedCrossRef
Chen, G., & Goeddel, D. V. (2002). TNF-R1 signaling: A beautiful pathway. Science, 296, 1634–1635.PubMedCrossRef
Chen, L. Z., Hochwald, G. M., Huang, C., Dakin, G., Tao, H., Cheng, C., et al. (1998). Gene therapy in allergic encephalomyelitis using myelin basic protein-specific T cells engineered to express latent transforming growth factor-beta1. Proceedings of the National Academy of Sciences of the United States of America, 95, 12516–12521.PubMedCrossRef
Chen, Y., Kuchroo, V. K., Inobe, J., Hafler, D. A., & Weiner, H. L. (1994). Regulatory T cell clones induced by oral tolerance: Suppression of autoimmune encephalomyelitis. Science, 265, 1237–1240.PubMedCrossRef
Chitnis, T., Najafian, N., Benou, C., Salama, A. D., Grusby, M. J., Sayegh, M. H., et al. (2001). Effect of targeted disruption of STAT4 and STAT6 on the induction of experimental autoimmune encephalomyelitis. Journal of Clinical Investigation, 108, 739–747.PubMed
Clerico, M., Contessa, G., & Durelli, L. (2007). Interferon-beta1a for the treatment of multiple sclerosis. Expert Opinion on Biological Therapy, 7, 535–542.PubMedCrossRef
Constantinescu, C. S., Goodman, D. B., Hilliard, B., Wysocka, M., & Cohen, J. A. (2000). Murine macrophages stimulated with central and peripheral nervous system myelin or purified myelin proteins release inflammatory products. Neuroscience Letters, 287, 171–174.PubMedCrossRef
Constantinescu, C. S., Wysocka, M., Hilliard, B., Ventura, E. S., Lavi, E., Trinchieri, G., et al. (1998). Antibodies against IL-12 prevent superantigen-induced and spontaneous relapses of experimental autoimmune encephalomyelitis. Journal of Immunology, 161, 5097–5104.
Crisi, G. M., Santambrogio, L., Hochwald, G. M., Smith, S. R., Carlino, J. A., & Thorbecke, G. J. (1995). Staphylococcal enterotoxin B and tumor-necrosis factor-alpha-induced relapses of experimental allergic encephalomyelitis: Protection by transforming growth factor-beta and interleukin-10. European Journal of Immunology, 25, 3035–3040.PubMedCrossRef
Cua, D. J., Hinton, D. R., & Stohlman, S. A. (1995). Self-antigen-induced Th2 responses in experimental allergic encephalomyelitis (EAE)-resistant mice. Th2-mediated suppression of autoimmune disease. Journal of Immunology, 155, 4052–4059.
Cua, D., Sherlock, J., Chen, Y., Murphy, C., Joyce, B., Seymour, B., et al. (2003). Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature, 421, 744–748.PubMedCrossRef
D’Souza, S. D., Bonetti, B., Balasingam, V., Cashman, N. R., Barker, P. A., Troutt, A. B., et al. (1996). Multiple sclerosis: Fas signaling in oligodendrocyte cell death. Journal of Experimental Medicine, 184, 2361–2370.PubMedCrossRef
da Cunha, A., & Vitkovic, L. (1992). Transforming growth factor-beta 1 (TGF-beta 1) expression and regulation in rat cortical astrocytes. Journal of Neuroimmunology, 36, 157–169.PubMedCrossRef
Dal Canto, M. C., & Lipton, H. L. (1975). Primary demyelination in Theiler’s virus infection. An ultrastructural study. Laboratory Investigation, 33, 626–637.PubMed
De Groot, C. J., Montagne, L., Barten, A. D., Sminia, P., & Van Der Valk, P. (1999). Expression of transforming growth factor (TGF)-beta1, -beta2, and -beta3 isoforms and TGF-beta type I and type II receptors in multiple sclerosis lesions and human adult astrocyte cultures. Journal of Neuropathology and Experimental Neurology, 58, 174–187.PubMedCrossRef
de Herve, M. G., Delfraissy, J. F., & Taoufik, Y. (2001). Following direct CD40 activation, human primary microglial cells produce IL-12 p40 but not bioactive IL-12 p70. Cytokine, 14, 88–96.CrossRef
De Simone, R., Ambrosini, E., Carnevale, D., Ajmone-Cat, M. A., & Minghetti, L. (2007). NGF promotes microglial migration through the activation of its high affinity receptor: Modulation by TGF-beta. Journal of Neuroimmunology, 190, 53–60.PubMedCrossRef
Deckert-Schluter, M., Bluethmann, H., Kaefer, N., Rang, A., & Schluter, D. (1999). Interferon-gamma receptor-mediated but not tumor necrosis factor receptor type 1- or type 2-mediated signaling is crucial for the activation of cerebral blood vessel endothelial cells and microglia in murine Toxoplasma encephalitis. American Journal of Pathology, 154, 1549–1561.PubMed
Dendorfer, U., Oettgen, P., & Libermann, T. A. (1994). Multiple regulatory elements in the interleukin-6 gene mediate induction by prostaglandins, cyclic AMP, and lipopolysaccharide. Molecular and Cellular Biology, 14, 4443–4454.PubMed
Dheen, S. T., Kaur, C., & Ling, E. A. (2007). Microglial activation and its implications in the brain diseases. Current Medicinal Chemistry, 14, 1189–1197.PubMedCrossRef
Dinarello, C. A., Cannon, J. G., Wolff, S. M., Bernheim, H. A., Beutler, B., Cerami, A., et al. (1986). Tumor necrosis factor (cachectin) is an endogenous pyrogen and induces production of interleukin 1. Journal of Experimental Medicine, 163, 1433–1450.PubMedCrossRef
Dower, S. K., Kronheim, S. R., Hopp, T. P., Cantrell, M., Deeley, M., Gillis, S., et al. (1986). The cell surface receptors for interleukin-1 alpha and interleukin-1 beta are identical. Nature, 324, 266–268.PubMedCrossRef
Dower, S. K., Kronheim, S. R., March, C. J., Conlon, P. J., Hopp, T. P., Gillis, S., et al. (1985). Detection and characterization of high affinity plasma membrane receptors for human interleukin 1. Journal of Experimental Medicine, 162, 501–515.PubMedCrossRef
Dowling, P., Shang, G., Raval, S., Menonna, J., Cook, S., & Husar, W. (1996). Involvement of the CD95 (APO-1/Fas) receptor/ligand system in multiple sclerosis brain. Journal of Experimental Medicine, 184, 1513–1518.PubMedCrossRef
Drescher, K. M., Murray, P. D., Lin, X., Carlino, J. A., & Rodriguez, M. (2000). TGF-beta 2 reduces demyelination, virus antigen expression, and macrophage recruitment in a viral model of multiple sclerosis. Journal of Immunology, 164, 3207–3213.
Dunne, A. and O’Neill L. A. (2003) The interleukin-1 receptor/Toll-like receptor superfamily: Signal transduction during inflammation and host defense. Sci STKE 2003, re3.
Duong, T. T., Finkelman, F. D., Singh, B., & Strejan, G. H. (1994). Effect of anti-interferon-gamma monoclonal antibody treatment on the development of experimental allergic encephalomyelitis in resistant mouse strains. Journal of Neuroimmunology, 53, 101–107.PubMedCrossRef
Duong, T. T., St Louis, J., Gilbert, J. J., Finkelman, F. D., & Strejan, G. H. (1992). Effect of anti-interferon-gamma and anti-interleukin-2 monoclonal antibody treatment on the development of actively and passively induced experimental allergic encephalomyelitis in the SJL/J mouse. Journal of Neuroimmunology, 36, 105–115.PubMedCrossRef
Emery, B., Cate, H. S., Marriott, M., Merson, T., Binder, M. D., Snell, C., et al. (2006). Suppressor of cytokine signaling 3 limits protection of leukemia inhibitory factor receptor signaling against central demyelination. Proceedings of the National Academy of Sciences of the United States of America, 103, 7859–7864.PubMedCrossRef
Erb, K. J., Ruger, B., von Brevern, M., Ryffel, B., Schimpl, A., & Rivett, K. (1997). Constitutive expression of interleukin (IL)-4 in vivo causes autoimmune-type disorders in mice. Journal of Experimental Medicine, 185, 329–339.PubMedCrossRef
Fabry, Z., Topham, D. J., Fee, D., Herlein, J., Carlino, J. A., Hart, M. N., et al. (1995). TGF-beta 2 decreases migration of lymphocytes in vitro and homing of cells into the central nervous system in vivo. Journal of Immunology, 155, 325–332.
Falcone, M., Rajan, A. J., Bloom, B. R., & Brosnan, C. F. (1998). A critical role for IL-4 in regulating disease severity in experimental allergic encephalomyelitis as demonstrated in IL-4-deficient C57BL/6 mice and BALB/c mice. Journal of Immunology, 160, 4822–4830.
Fantini, M. C., Becker, C., Monteleone, G., Pallone, F., Galle, P. R., & Neurath, M. F. (2004). Cutting edge: TGF-beta induces a regulatory phenotype in CD4 + CD25- T cells through Foxp3 induction and down-regulation of Smad7. Journal of Immunology, 172, 5149–5153.
Farina, C., Aloisi, F., & Meinl, E. (2007). Astrocytes are active players in cerebral innate immunity. Trends in Immunology, 28, 138–145.PubMedCrossRef
Fassbender, K., Ragoschke, A., Rossol, S., Schwartz, A., Mielke, O., Paulig, A., et al. (1998). Increased release of interleukin-12p40 in MS: Association with intracerebral inflammation. Neurology, 51, 753–758.PubMed
Fazakerley, J. K., & Walker, R. (2003). Virus demyelination. Journal of Neurovirology, 9, 148–164.PubMed
Ferber, I. A., Brocke, S., Taylor-Edwards, C., Ridgway, W., Dinisco, C., Steinman, L., et al. (1996). Mice with a disrupted IFN-gamma gene are susceptible to the induction of experimental autoimmune encephalomyelitis (EAE). Journal of Immunology, 156, 5–7.
Ferguson, B., Matyszak, M. K., Esiri, M. M., & Perry, V. H. (1997). Axonal damage in acute multiple sclerosis lesions. Brain, 120(Pt 3), 393–399.PubMedCrossRef
Ferrari, C. C., Depino, A. M., Prada, F., Muraro, N., Campbell, S., Podhajcer, O., et al. (2004). Reversible demyelination, blood-brain barrier breakdown, and pronounced neutrophil recruitment induced by chronic IL-1 expression in the brain. American Journal of Pathology, 165, 1827–1837.PubMed
Fischer, H. G., Bielinsky, A. K., Nitzgen, B., Daubener, W., & Hadding, U. (1993). Functional dichotomy of mouse microglia developed in vitro: Differential effects of macrophage and granulocyte/macrophage colony-stimulating factor on cytokine secretion and antitoxoplasmic activity. Journal of Neuroimmunology, 45, 193–201.PubMedCrossRef
Flowers, L. O., Johnson, H. M., Mujtaba, M. G., Ellis, M. R., Haider, S. M., & Subramaniam, P. S. (2004). Characterization of a peptide inhibitor of Janus kinase 2 that mimics suppressor of cytokine signaling 1 function. Journal of Immunology, 172, 7510–7518.
Fontenot, J. D., Gavin, M. A., & Rudensky, A. Y. (2003). Foxp3 programs the development and function of CD4 + CD25 + regulatory T cells. Nature Immunology, 4, 330–336.PubMedCrossRef
Foote, A. K., & Blakemore, W. F. (2005). Inflammation stimulates remyelination in areas of chronic demyelination. Brain, 128, 528–539.PubMedCrossRef
Franklin, R. J., & ffrench-Constant, C. (2008). Remyelination in the CNS: From biology to therapy. Nature Reviews Neuroscience, 9, 839–855.PubMedCrossRef
Frei, K., Eugster, H. P., Bopst, M., Constantinescu, C. S., Lavi, E., & Fontana, A. (1997). Tumor necrosis factor alpha and lymphotoxin alpha are not required for induction of acute experimental autoimmune encephalomyelitis. Journal of Experimental Medicine, 185, 2177–2182.PubMedCrossRef
Frei, K., Fredrikson, S., Fontana, A., & Link, H. (1991). Interleukin-6 is elevated in plasma in multiple sclerosis. Journal of Neuroimmunology, 31, 147–153.PubMedCrossRef
Friedman, W. J., Thakur, S., Seidman, L., & Rabson, A. B. (1996). Regulation of nerve growth factor mRNA by interleukin-1 in rat hippocampal astrocytes is mediated by NFkappaB. Journal of Biological Chemistry, 271, 31115–31120.PubMedCrossRef
Furlan, R., Poliani, P. L., Galbiati, F., Bergami, A., Grimaldi, L. M., Comi, G., et al. (1998). Central nervous system delivery of interleukin 4 by a nonreplicative herpes simplex type 1 viral vector ameliorates autoimmune demyelination. Human Gene Therapy, 9, 2605–2617.PubMedCrossRef
Gallo, V., & Armstrong, R. C. (2008). Myelin repair strategies: A cellular view. Current Opinion in Neurology, 21, 278–283.PubMedCrossRef
Gao, X., Gillig, T. A., Ye, P., D’Ercole, A. J., Matsushima, G. K., & Popko, B. (2000). Interferon-gamma protects against cuprizone-induced demyelination. Molecular and Cellular Neurosciences, 16, 338–349.PubMedCrossRef
Gaupp, S., Cannella, B., & Raine, C. S. (2008). Amelioration of experimental autoimmune encephalomyelitis in IL-4Ralpha-/- mice implicates compensatory up-regulation of Th2-type cytokines. American Journal of Pathology, 173, 119–129.PubMedCrossRef
Germann, T., Gately, M. K., Schoenhaut, D. S., Lohoff, M., Mattner, F., Fischer, S., et al. (1993). Interleukin-12/T cell stimulating factor, a cytokine with multiple effects on T helper type 1 (Th1) but not on Th2 cells. European Journal of Immunology, 23, 1762–1770.PubMedCrossRef
Gijbels, K., Brocke, S., Abrams, J. S., & Steinman, L. (1995). Administration of neutralizing antibodies to interleukin-6 (IL-6) reduces experimental autoimmune encephalomyelitis and is associated with elevated levels of IL-6 bioactivity in central nervous system and circulation. Molecular Medicine, 1, 795–805.PubMed
Gil-Guerrero, L., Dotor, J., Huibregtse, I. L., Casares, N., Lopez-Vazquez, A. B., Rudilla, F., et al. (2008). In vitro and in vivo down-regulation of regulatory T cell activity with a peptide inhibitor of TGF-beta1. Journal of Immunology, 181, 126–135.
Giulian, D., Johnson, B., Krebs, J. F., George, J. K., & Tapscott, M. (1991). Microglial mitogens are produced in the developing and injured mammalian brain. Journal of Cell Biology, 112, 323–333.PubMedCrossRef
Giulian, D., & Lachman, L. B. (1985). Interleukin-1 stimulation of astroglial proliferation after brain injury. Science, 228, 497–499.PubMedCrossRef
Gold, R. (2006). Understanding pathogenesis and therapy of multiple sclerosis via animal models: 70 years of merits and culprits in experimental autoimmune encephalomyelitis research. Brain, 129, 1953–1971.PubMedCrossRef
Gough, D. J., Levy, D. E., Johnstone, R. W., & Clarke, C. J. (2008). IFNgamma signaling-does it mean JAK-STAT? Cytokine and Growth Factor Reviews, 19, 383–394.PubMedCrossRef
Gran, B., Zhang, G. X., Yu, S., Li, J., Chen, X. H., Ventura, E. S., et al. (2002). IL-12p35-deficient mice are susceptible to experimental autoimmune encephalomyelitis: Evidence for redundancy in the IL-12 system in the induction of central nervous system autoimmune demyelination. Journal of Immunology, 169, 7104–7110.
Greenfeder, S. A., Nunes, P., Kwee, L., Labow, M., Chizzonite, R. A., & Ju, G. (1995). Molecular cloning and characterization of a second subunit of the interleukin 1 receptor complex. Journal of Biological Chemistry, 270, 13757–13765.PubMedCrossRef
Grommes, C., Lee, C. Y., Wilkinson, B. L., Jiang, Q., Koenigsknecht-Talboo, J. L., Varnum, B., et al. (2008). Regulation of microglial phagocytosis and inflammatory gene expression by Gas6 acting on the Axl/Mer family of tyrosine kinases. Journal of Neuroimmune Pharmacology, 3, 130–140.PubMedCrossRef
Guha, M., & Mackman, N. (2001). LPS induction of gene expression in human monocytes. Cellular Signalling, 13, 85–94.PubMedCrossRef
Guo, B., Chang, E., & Cheng, G. (2008). The type I IFN induction pathway constrains Th17-mediated autoimmune inflammation in mice. Journal of Clinical Investigation, 118, 1680–1690.PubMedCrossRef
Haak, S., Croxford, A. L., Kreymborg, K., Heppner, F. L., Pouly, S., Becher, B., et al. (2009). IL-17A and IL-17F do not contribute vitally to autoimmune neuro-inflammation in mice. Journal of Clinical Investigation, 119, 61–69.PubMed
Hall, S. M. (1972). The effect of injections of lysophosphatidyl choline into white matter of the adult mouse spinal cord. Journal of Cell Science, 10, 535–546.PubMed
Hallenbeck, J. M. (2002). The many faces of tumor necrosis factor in stroke. Nature Medicine, 8, 1363–1368.PubMedCrossRef
Hauser, S. L., Doolittle, T. H., Lincoln, R., Brown, R. H., & Dinarello, C. A. (1990). Cytokine accumulations in CSF of multiple sclerosis patients: Frequent detection of interleukin-1 and tumor necrosis factor but not interleukin-6. Neurology, 40, 1735–1739.PubMed
Healy, A. M., Schwartz, J. J., Zhu, X., Herrick, B. E., Varnum, B., & Farber, H. W. (2001). Gas 6 promotes Axl-mediated survival in pulmonary endothelial cells. American Journal of Physiology Lung Cellular and Molecular Physiology, 280, L1273–L1281.PubMed
Hebenstreit, D., Wirnsberger, G., Horejs-Hoeck, J., & Duschl, A. (2006). Signaling mechanisms, interaction partners, and target genes of STAT6. Cytokine and Growth Factor Reviews, 17, 173–188.PubMedCrossRef
Heine, S., Ebnet, J., Maysami, S., & Stangel, M. (2006). Effects of interferon-beta on oligodendroglial cells. Journal of Neuroimmunology, 177, 173–180.PubMedCrossRef
Held, W., Meyermann, R., Qin, Y., & Mueller, C. (1993). Perforin and tumor necrosis factor alpha in the pathogenesis of experimental allergic encephalomyelitis: Comparison of autoantigen induced and transferred disease in Lewis rats. Journal of Autoimmunity, 6, 311–322.PubMedCrossRef
Hemmi, S., Böhln, R., Stark, G., Di Marco, F., & Aguet, M. (1994). A novel member of the interferon receptor family complements functionality of the murine interferon γ receptor in human cells. Cell, 76, 803–810.PubMedCrossRef
Hendriks, J. J., Slaets, H., Carmans, S., de Vries, H. E., Dijkstra, C. D., Stinissen, P., et al. (2008). Leukemia inhibitory factor modulates production of inflammatory mediators and myelin phagocytosis by macrophages. Journal of Neuroimmunology, 204, 52–57.PubMedCrossRef
Hendriks, J. J., Teunissen, C. E., de Vries, H. E., & Dijkstra, C. D. (2005). Macrophages and neurodegeneration. Brain Research. Brain Research Reviews, 48, 185–195.PubMedCrossRef
Heppner, F. L., Greter, M., Marino, D., Falsig, J., Raivich, G., Hovelmeyer, N., et al. (2005). Experimental autoimmune encephalomyelitis repressed by microglial paralysis. Nature Medicine, 11, 146–152.PubMedCrossRef
Herrera-Molina, R., & von Bernhardi, R. (2005). Transforming growth factor-beta 1 produced by hippocampal cells modulates microglial reactivity in culture. Neurobiology of Diseases, 19, 229–236.CrossRef
Hershkoviz, R., Mor, F., Gilat, D., Cohen, I. R., & Lider, O. (1992). T cells in the spinal cord in experimental autoimmune encephalomyelitis are matrix adherent and secrete tumor necrosis factor alpha. Journal of Neuroimmunology, 37, 161–166.PubMedCrossRef
Heyen, J. R., Ye, S., Finck, B. N., & Johnson, R. W. (2000). Interleukin (IL)-10 inhibits IL-6 production in microglia by preventing activation of NF-kappaB. Brain Research. Molecular Brain Research, 77, 138–147.PubMedCrossRef
Hinks, G. L., & Franklin, R. J. (1999). Distinctive patterns of PDGF-A, FGF-2, IGF-I, and TGF-beta1 gene expression during remyelination of experimentally-induced spinal cord demyelination. Molecular and Cellular Neurosciences, 14, 153–168.PubMedCrossRef
Hinks, G. L., & Franklin, R. J. (2000). Delayed changes in growth factor gene expression during slow remyelination in the CNS of aged rats. Molecular and Cellular Neurosciences, 16, 542–556.PubMedCrossRef
Hiscott, J., Marois, J., Garoufalis, J., D’Addario, M., Roulston, A., Kwan, I., et al. (1993). Characterization of a functional NF-kappa B site in the human interleukin 1 beta promoter: Evidence for a positive autoregulatory loop. Molecular and Cellular Biology, 13, 6231–6240.PubMed
Hoehn, H. J., Kress, Y., Sohn, A., Brosnan, C. F., Bourdon, S., & Shafit-Zagardo, B. (2008). Axl-/- mice have delayed recovery and prolonged axonal damage following cuprizone toxicity. Brain Research, 1240, 1–11.PubMedCrossRef
Hofman, F. M., Hinton, D. R., Johnson, K., & Merrill, J. E. (1989). Tumor necrosis factor identified in multiple sclerosis brain. Journal of Experimental Medicine, 170, 607–612.PubMedCrossRef
Hofman, F. M., von Hanwehr, R. I., Dinarello, C. A., Mizel, S. B., Hinton, D., & Merrill, J. E. (1986). Immunoregulatory molecules and IL 2 receptors identified in multiple sclerosis brain. Journal of Immunology, 136, 3239–3245.
Hori, S., Nomura, T., & Sakaguchi, S. (2003). Control of regulatory T cell development by the transcription factor Foxp3. Science, 299, 1057–1061.PubMedCrossRef
Horvath, C. M. (2004) The Jak-STAT pathway stimulated by interferon gamma. Sci STKE 2004, tr8.
Hoshino, K., Kaisho, T., Iwabe, T., Takeuchi, O., & Akira, S. (2002). Differential involvement of IFN-beta in Toll-like receptor-stimulated dendritic cell activation. International Immunology, 14, 1225–1231.PubMedCrossRef
Hövelmeyer, N., Hao, Z., Kranidioti, K., Kassiotis, G., Buch, T., Frommer, F., et al. (2005). Apoptosis of oligodendrocytes via Fas and TNF-R1 is a key event in the induction of experimental autoimmune encephalomyelitis. Journal of Immunology, 175, 5875–5884.
Hsieh, J. (2004). IGF-I instructs multipotent adult neural progenitor cells to become oligodendrocytes. Journal of Cell Biology, 164, 111–122.PubMedCrossRef
Huber, M., Steinwald, V., Guralnik, A., Brustle, A., Kleemann, P., Rosenplanter, C., et al. (2008). IL-27 inhibits the development of regulatory T cells via STAT3. International Immunology, 20, 223–234.PubMedCrossRef
Hunter, C. A. (2005). New IL-12-family members: IL-23 and IL-27, cytokines with divergent functions. Nature Reviews Immunology, 5, 521–531.PubMedCrossRef
Ichikawa, M., Koh, C. S., Inoue, A., Tsuyusaki, J., Yamazaki, M., Inaba, Y., et al. (2000). Anti-IL-12 antibody prevents the development and progression of multiple sclerosis-like relapsing–remitting demyelinating disease in NOD mice induced with myelin oligodendrocyte glycoprotein peptide. Journal of Neuroimmunology, 102, 56–66.PubMedCrossRef
Irvine, K., & Blakemore, W. (2008). Remyelination protects axons from demyelination-associated axon degeneration. Brain, 131, 1464–1477.PubMedCrossRef
Issazadeh, S., Ljungdahl, A., Hojeberg, B., Mustafa, M., & Olsson, T. (1995). Cytokine production in the central nervous system of Lewis rats with experimental autoimmune encephalomyelitis: Dynamics of mRNA expression for interleukin-10, interleukin-12, cytolysin, tumor necrosis factor alpha and tumor necrosis factor beta. Journal of Neuroimmunology, 61, 205–212.PubMedCrossRef
Jana, M., Dasgupta, S., Pal, U., & Pahan, K. (2009). IL-12 p40 homodimer, the so-called biologically inactive molecule, induces nitric oxide synthase in microglia via IL-12R beta 1. Glia, 57, 1553–1565.PubMedCrossRef
Jana, M., Dasgupta, S., Saha, R. N., Liu, X., & Pahan, K. (2003). Induction of tumor necrosis factor-alpha (TNF-alpha) by interleukin-12 p40 monomer and homodimer in microglia and macrophages. Journal of Neurochemistry, 86, 519–528.PubMedCrossRef
Jana, M., Liu, X., Koka, S., Ghosh, S., Petro, T. M., & Pahan, K. (2001). Ligation of CD40 stimulates the induction of nitric-oxide synthase in microglial cells. Journal of Biological Chemistry, 276, 44527–44533.PubMedCrossRef
Jana, M., & Pahan, K. (2009a). IL-12 p40 homodimer, but not IL-12 p70, induces the expression of IL-16 in microglia and macrophages. Molecular Immunology, 46, 773–783.PubMedCrossRef
Jana, M., & Pahan, K. (2009b). Induction of lymphotoxin-alpha by interleukin-12 p40 homodimer, the so-called biologically inactive molecule, but not IL-12 p70. Immunology, 127, 312–325.PubMedCrossRef
Jander, S., Pohl, J., D’Urso, D., Gillen, C., & Stoll, G. (1998). Time course and cellular localization of interleukin-10 mRNA and protein expression in autoimmune inflammation of the rat central nervous system. American Journal of Pathology, 152, 975–982.PubMed
Jang, S., Kelley, K. W., & Johnson, R. W. (2008). Luteolin reduces IL-6 production in microglia by inhibiting JNK phosphorylation and activation of AP-1. Proceedings of the National Academy of Sciences of the United States of America, 105, 7534–7539.PubMedCrossRef
Jeohn, G. H., Kong, L. Y., Wilson, B., Hudson, P., & Hong, J. S. (1998). Synergistic neurotoxic effects of combined treatments with cytokines in murine primary mixed neuron/glia cultures. Journal of Neuroimmunology, 85, 1–10.PubMedCrossRef
Jin, Y. H., Mohindru, M., Kang, M. H., Fuller, A. C., Kang, B., Gallo, D., et al. (2007). Differential virus replication, cytokine production, and antigen-presenting function by microglia from susceptible and resistant mice infected with Theiler’s virus. Journal of Virology, 81, 11690–11702.PubMedCrossRef
John, G. R., Shankar, S. L., Shafit-Zagardo, B., Massimi, A., Lee, S. C., Raine, C. S., et al. (2002). Multiple sclerosis: Re-expression of a developmental pathway that restricts oligodendrocyte maturation. Nature Medicine, 8, 1115–1121.PubMedCrossRef
Johns, L. D., Flanders, K. C., Ranges, G. E., & Sriram, S. (1991). Successful treatment of experimental allergic encephalomyelitis with transforming growth factor-beta 1. Journal of Immunology, 147, 1792–1796.
Johns, L. D., & Sriram, S. (1993). Experimental allergic encephalomyelitis: Neutralizing antibody to TGF beta 1 enhances the clinical severity of the disease. Journal of Neuroimmunology, 47, 1–7.PubMedCrossRef
Josefowicz, S. Z., & Rudensky, A. (2009). Control of regulatory T cell lineage commitment and maintenance. Immunity, 30, 616–625.PubMedCrossRef
Kamiya, S., Owaki, T., Morishima, N., Fukai, F., Mizuguchi, J., & Yoshimoto, T. (2004). An indispensable role for STAT1 in IL-27-induced T-bet expression but not proliferation of naive CD4 + T cells. Journal of Immunology, 173, 3871–3877.
Katz-Levy, Y., Neville, K. L., Padilla, J., Rahbe, S., Begolka, W. S., Girvin, A. M., et al. (2000). Temporal development of autoreactive Th1 responses and endogenous presentation of self myelin epitopes by central nervous system-resident APCs in Theiler’s virus-infected mice. Journal of Immunology, 165, 5304–5314.
Kawanokuchi, J., Mizuno, T., Kato, H., Mitsuma, N., & Suzumura, A. (2004). Effects of interferon-beta on microglial functions as inflammatory and antigen presenting cells in the central nervous system. Neuropharmacology, 46, 734–742.PubMedCrossRef
Kawanokuchi, J., Shimizu, K., Nitta, A., Yamada, K., Mizuno, T., Takeuchi, H., et al. (2008). Production and functions of IL-17 in microglia. Journal of Neuroimmunology, 194, 54–61.PubMedCrossRef
Keating, P., O’Sullivan, D., Tierney, J. B., Kenwright, D., Miromoeini, S., Mawasse, L., et al. (2009). Protection from EAE by IL-4Ralpha(-/-) macrophages depends upon T regulatory cell involvement. Immunology and Cell Biology, 87, 534–545.PubMedCrossRef
Kennedy, M. K., Torrance, D. S., Picha, K. S., & Mohler, K. M. (1992). Analysis of cytokine mRNA expression in the central nervous system of mice with experimental autoimmune encephalomyelitis reveals that IL-10 mRNA expression correlates with recovery. Journal of Immunology, 149, 2496–2505.
Kerr, B. J., & Patterson, P. H. (2005). Leukemia inhibitory factor promotes oligodendrocyte survival after spinal cord injury. Glia, 51, 73–79.PubMedCrossRef
Kiefer, R., Schweitzer, T., Jung, S., Toyka, K. V., & Hartung, H. P. (1998). Sequential expression of transforming growth factor-beta1 by T-cells, macrophages, and microglia in rat spinal cord during autoimmune inflammation. Journal of Neuropathology and Experimental Neurology, 57, 385–395.PubMedCrossRef
Kim, B. S., Palma, J. P., Kwon, D., & Fuller, A. C. (2005). Innate immune response induced by Theiler’s murine encephalomyelitis virus infection. Immunologic Research, 31, 1–12.PubMedCrossRef
Kirwin, S. J., Dowdell, K. C., Hindinger, C., Feng, N., Bergmann, C. C., Hinton, D. R., et al. (2006). Altered neuroantigen-specific cytokine secretion in a Th2 environment reduces experimental autoimmune encephalomyelitis. Journal of Neuroimmunology, 178, 30–39.PubMedCrossRef
Kohji, T., & Matsumoto, Y. (2000). Coexpression of Fas/FasL and Bax on brain and infiltrating T cells in the central nervous system is closely associated with apoptotic cell death during autoimmune encephalomyelitis. Journal of Neuroimmunology, 106, 165–171.PubMedCrossRef
Kohm, A. P., Carpentier, P. A., Anger, H. A., & Miller, S. D. (2002). Cutting edge: CD4+CD25+ regulatory T cells suppress antigen-specific autoreactive immune responses and central nervous system inflammation during active experimental autoimmune encephalomyelitis. Journal of Immunology, 169, 4712–4716.
Koizumi, S., Shigemoto-Mogami, Y., Nasu-Tada, K., Shinozaki, Y., Ohsawa, K., Tsuda, M., et al. (2007). UDP acting at P2Y6 receptors is a mediator of microglial phagocytosis. Nature, 446, 1091–1095.PubMedCrossRef
Korner, H., Goodsall, A. L., Lemckert, F. A., Scallon, B. J., Ghrayeb, J., Ford, A. L., et al. (1995). Unimpaired autoreactive T-cell traffic within the central nervous system during tumor necrosis factor receptor-mediated inhibition of experimental autoimmune encephalomyelitis. Proceedings of the National Academy of Sciences of the United States of America, 92, 11066–11070.PubMedCrossRef
Kotter, M. R., Li, W. W., Zhao, C., & Franklin, R. J. (2006). Myelin impairs CNS remyelination by inhibiting oligodendrocyte precursor cell differentiation. Journal of Neuroscience, 26, 328–332.PubMedCrossRef
Kotter, M. R., Setzu, A., Sim, F. J., Van Rooijen, N., & Franklin, R. J. (2001). Macrophage depletion impairs oligodendrocyte remyelination following lysolecithin-induced demyelination. Glia, 35, 204–212.PubMedCrossRef
Kotter, M. R., Zhao, C., van Rooijen, N., & Franklin, R. J. (2005). Macrophage-depletion induced impairment of experimental CNS remyelination is associated with a reduced oligodendrocyte progenitor cell response and altered growth factor expression. Neurobiology of Diseases, 18, 166–175.CrossRef
Krady, J. K., Lin, H. W., Liberto, C. M., Basu, A., Kremlev, S. G., & Levison, S. W. (2008). Ciliary neurotrophic factor and interleukin-6 differentially activate microglia. Journal of Neuroscience Research, 86, 1538–1547.PubMedCrossRef
Krakowski, M., & Owens, T. (1996). Interferon-gamma confers resistance to experimental allergic encephalomyelitis. European Journal of Immunology, 26, 1641–1646.PubMedCrossRef
Kroenke, M. A., Carlson, T. J., Andjelkovic, A. V., & Segal, B. M. (2008). IL-12- and IL-23-modulated T cells induce distinct types of EAE based on histology, CNS chemokine profile, and response to cytokine inhibition. Journal of Experimental Medicine, 205, 1535–1541.PubMedCrossRef
Kuroda, Y., & Shimamoto, Y. (1991). Human tumor necrosis factor-alpha augments experimental allergic encephalomyelitis in rats. Journal of Neuroimmunology, 34, 159–164.PubMedCrossRef
Kuruvilla, A. P., Shah, R., Hochwald, G. M., Liggitt, H. D., Palladino, M. A., & Thorbecke, G. J. (1991). Protective effect of transforming growth factor beta 1 on experimental autoimmune diseases in mice. Proceedings of the National Academy of Sciences of the United States of America, 88, 2918–2921.PubMedCrossRef
Kwidzinski, E., Bunse, J., Aktas, O., Richter, D., Mutlu, L., Zipp, F., et al. (2005). Indolamine 2, 3-dioxygenase is expressed in the CNS and down-regulates autoimmune inflammation. The FASEB Journal, 19, 1347–1349.PubMed
Kwidzinski, E., Bunse, J., Kovac, A. D., Ullrich, O., Zipp, F., Nitsch, R., et al. (2003). IDO (indolamine 2, 3-dioxygenase) expression and function in the CNS. Advances in Experimental Medicine and Biology, 527, 113–118.PubMed
Labow, M., Shuster, D., Zetterstrom, M., Nunes, P., Terry, R., Cullinan, E. B., et al. (1997). Absence of IL-1 signaling and reduced inflammatory response in IL-1 type I receptor-deficient mice. Journal of Immunology, 159, 2452–2461.
Lalancette-Hebert, M., Gowing, G., Simard, A., Weng, Y. C., & Kriz, J. (2007). Selective ablation of proliferating microglial cells exacerbates ischemic injury in the brain. Journal of Neuroscience, 27, 2596–2605.PubMedCrossRef
Lalive, P. H., Paglinawan, R., Biollaz, G., Kappos, E. A., Leone, D. P., Malipiero, U., et al. (2005). TGF-beta-treated microglia induce oligodendrocyte precursor cell chemotaxis through the HGF-c-Met pathway. European Journal of Immunology, 35, 727–737.PubMedCrossRef
Langrish, C. L., Chen, Y., Blumenschein, W. M., Mattson, J., Basham, B., Sedgwick, J. D., et al. (2005). IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. Journal of Experimental Medicine, 201, 233–240.PubMedCrossRef
Langrish, C. L., McKenzie, B. S., Wilson, N. J., de Waal Malefyt, R., Kastelein, R. A., & Cua, D. J. (2004). IL-12 and IL-23: Master regulators of innate and adaptive immunity. Immunological Reviews, 202, 96–105.PubMedCrossRef
Lassmann, H. (2008). Mechanisms of inflammation induced tissue injury in multiple sclerosis. Journal of the Neurological Sciences, 274, 45–47.PubMedCrossRef
Lassmann, H., Bruck, W., Lucchinetti, C., & Rodriguez, M. (1997). Remyelination in multiple sclerosis. Multiple Sclerosis, 3, 133–136.PubMedCrossRef
Ledeboer, A., Breve, J. J., Poole, S., Tilders, F. J., & Van Dam, A. M. (2000). Interleukin-10, interleukin-4, and transforming growth factor-beta differentially regulate lipopolysaccharide-induced production of pro-inflammatory cytokines and nitric oxide in co-cultures of rat astroglial and microglial cells. Glia, 30, 134–142.PubMedCrossRef
Ledeboer, A., Breve, J. J., Wierinckx, A., van der Jagt, S., Bristow, A. F., Leysen, J. E., et al. (2002). Expression and regulation of interleukin-10 and interleukin-10 receptor in rat astroglial and microglial cells. European Journal of Neuroscience, 16, 1175–1185.PubMedCrossRef
Lee, W. P., Liao, Y., Robinson, D., Kung, H. J., Liu, E. T., & Hung, M. C. (1999). Axl-gas6 interaction counteracts E1A-mediated cell growth suppression and proapoptotic activity. Molecular and Cellular Biology, 19, 8075–8082.PubMed
Leonard, J. P., Waldburger, K. E., & Goldman, S. J. (1995). Prevention of experimental autoimmune encephalomyelitis by antibodies against interleukin 12. Journal of Experimental Medicine, 181, 381–386.PubMedCrossRef
Li, J., Baud, O., Vartanian, T., Volpe, J. J., & Rosenberg, P. A. (2005a). Peroxynitrite generated by inducible nitric oxide synthase and NADPH oxidase mediates microglial toxicity to oligodendrocytes. Proceedings of the National Academy of Sciences of the United States of America, 102, 9936–9941.PubMedCrossRef
Li, Y., Chu, N., Hu, A., Gran, B., Rostami, A., & Zhang, G. X. (2007). Increased IL-23p19 expression in multiple sclerosis lesions and its induction in microglia. Brain, 130, 490–501.PubMedCrossRef
Li, Y., Chu, N., Rostami, A., & Zhang, G. X. (2006a). Dendritic cells transduced with SOCS-3 exhibit a tolerogenic/DC2 phenotype that directs type 2 Th cell differentiation in vitro and in vivo. Journal of Immunology, 177, 1679–1688.
Li, J., Gran, B., Zhang, G. X., Rostami, A., & Kamoun, M. (2005b). IL-27 subunits and its receptor (WSX-1) mRNAs are markedly up-regulated in inflammatory cells in the CNS during experimental autoimmune encephalomyelitis. Journal of the Neurological Sciences, 232, 3–9.PubMedCrossRef
Li, W., Maeda, Y., Ming, X., Cook, S., Chapin, J., Husar, W., et al. (2002). Apoptotic death following Fas activation in human oligodendrocyte hybrid cultures. Journal of Neuroscience Research, 69, 189–196.PubMedCrossRef
Li, M. O., Wan, Y. Y., Sanjabi, S., Robertson, A. K., & Flavell, R. A. (2006b). Transforming growth factor-beta regulation of immune responses. Annual Review of Immunology, 24, 99–146.PubMedCrossRef
Li, M., Zhou, Y., Feng, G., & Su, S. B. (2009). The critical role of Toll-like receptor signaling pathways in the induction and progression of autoimmune diseases. Current Molecular Medicine, 9, 365–374.PubMedCrossRef
Lin, W., Kemper, A., Dupree, J. L., Harding, H. P., Ron, D., & Popko, B. (2006). Interferon-gamma inhibits central nervous system remyelination through a process modulated by endoplasmic reticulum stress. Brain, 129, 1306–1318.PubMedCrossRef
Lin, H. W., & Levison, S. W. (2009). Context-dependent IL-6 potentiation of interferon- gamma-induced IL-12 secretion and CD40 expression in murine microglia. Journal of Neurochemistry, 111, 808–818.PubMedCrossRef
Lin, M. W., Tsao, L. T., Chang, L. C., Chen, Y. L., Huang, L. J., Kuo, S. C., et al. (2007). Inhibition of lipopolysaccharide-stimulated NO production by a novel synthetic compound CYL-4d in RAW 264.7 macrophages involving the blockade of MEK4/JNK/AP-1 pathway. Biochemical Pharmacology, 73, 1796–1806.PubMedCrossRef
Lipton, H. L. (1975). Theiler’s virus infection in mice: An unusual biphasic disease process leading to demyelination. Infection and Immunity, 11, 1147–1155.PubMed
Lipton, H. L., Kumar, A. S., & Trottier, M. (2005). Theiler’s virus persistence in the central nervous system of mice is associated with continuous viral replication and a difference in outcome of infection of infiltrating macrophages versus oligodendrocytes. Virus Research, 111, 214–223.PubMedCrossRef
Liu, J., Marino, M. W., Wong, G., Grail, D., Dunn, A., Bettadapura, J., et al. (1998). TNF is a potent anti-inflammatory cytokine in autoimmune-mediated demyelination. Nature Medicine, 4, 78–83.PubMedCrossRef
Liu, Y., Teige, I., Ericsson, I., Navikas, V., and Issazadeh-Navikas, S. (2010) Suppression of EAE by oral tolerance is independent of endogenous IFN-beta whereas treatment with recombinant IFN-beta ameliorates EAE. Immunol Cell Biol. Jan 12 (Epub ahead of print).
Lodge, P. A., & Sriram, S. (1996). Regulation of microglial activation by TGF-beta, IL-10, and CSF-1. Journal of Leukocyte Biology, 60, 502–508.PubMed
Longbrake, E. E., & Racke, M. K. (2009). Why did IL-12/IL-23 antibody therapy fail in multiple sclerosis? Expert Review of Neurotherapeutics, 9, 319–321.PubMedCrossRef
Loughlin, A. J., Woodroofe, M. N., & Cuzner, M. L. (1993). Modulation of interferon-gamma-induced major histocompatibility complex class II and Fc receptor expression on isolated microglia by transforming growth factor-beta 1, interleukin-4, noradrenaline and glucocorticoids. Immunology, 79, 125–130.PubMed
Louis, J. C., Magal, E., Takayama, S., & Varon, S. (1993). CNTF protection of oligodendrocytes against natural and tumor necrosis factor-induced death. Science, 259, 689–692.PubMedCrossRef
Lovas, G., Szilagyi, N., Majtenyi, K., Palkovits, M., & Komoly, S. (2000). Axonal changes in chronic demyelinated cervical spinal cord plaques. Brain, 123(Pt 2), 308–317.PubMedCrossRef
Lowenstein, C. J., Alley, E. W., Raval, P., Snowman, A. M., Snyder, S. H., Russell, S. W., et al. (1993). Macrophage nitric oxide synthase gene: Two upstream regions mediate induction by interferon gamma and lipopolysaccharide. Proceedings of the National Academy of Sciences of the United States of America, 90, 9730–9734.PubMedCrossRef
Lucas, S., Ghilardi, N., Li, J., & de Sauvage, F. J. (2003). IL-27 regulates IL-12 responsiveness of naive CD4 + T cells through Stat1-dependent and -independent mechanisms. Proceedings of the National Academy of Sciences of the United States of America, 100, 15047–15052.PubMedCrossRef
Lucchinetti, C., Bruck, W., Parisi, J., Scheithauer, B., Rodriguez, M., & Lassmann, H. (1999). A quantitative analysis of oligodendrocytes in multiple sclerosis lesions. A study of 113 cases. Brain, 122(Pt 12), 2279–2295.PubMedCrossRef
Lucchinetti, C., Bruck, W., Parisi, J., Scheithauer, B., Rodriguez, M., & Lassmann, H. (2000). Heterogeneity of multiple sclerosis lesions: Implications for the pathogenesis of demyelination. Annals of Neurology, 47, 707–717.PubMedCrossRef
Lucchinetti, C. F., Bruck, W., Rodriguez, M., & Lassmann, H. (1996). Distinct patterns of multiple sclerosis pathology indicates heterogeneity on pathogenesis. Brain Pathology, 6, 259–274.PubMedCrossRef
Luo, J., Ho, P. P., Buckwalter, M. S., Hsu, T., Lee, L. Y., Zhang, H., et al. (2007). Glia-dependent TGF-beta signaling, acting independently of the TH17 pathway, is critical for initiation of murine autoimmune encephalomyelitis. Journal of Clinical Investigation, 117, 3306–3315.PubMedCrossRef
Magnus, T., Chan, A., Linker, R. A., Toyka, K. V., & Gold, R. (2002a). Astrocytes are less efficient in the removal of apoptotic lymphocytes than microglia cells: Implications for the role of glial cells in the inflamed central nervous system. Journal of Neuropathology and Experimental Neurology, 61, 760–766.PubMed
Magnus, T., Chan, A., Savill, J., Toyka, K. V., & Gold, R. (2002b). Phagocytotic removal of apoptotic, inflammatory lymphocytes in the central nervous system by microglia and its functional implications. Journal of Neuroimmunology, 130, 1–9.PubMedCrossRef
Maimone, D., Gregory, S., Arnason, B. G., & Reder, A. T. (1991). Cytokine levels in the cerebrospinal fluid and serum of patients with multiple sclerosis. Journal of Neuroimmunology, 32, 67–74.PubMedCrossRef
Maimone, D., Guazzi, G. C., & Annunziata, P. (1997). IL-6 detection in multiple sclerosis brain. Journal of the Neurological Sciences, 146, 59–65.PubMedCrossRef
Makwana, M., Jones, L. L., Cuthill, D., Heuer, H., Bohatschek, M., Hristova, M., et al. (2007). Endogenous transforming growth factor beta 1 suppresses inflammation and promotes survival in adult CNS. Journal of Neuroscience, 27, 11201–11213.PubMedCrossRef
Malipiero, U. V., Frei, K., & Fontana, A. (1990). Production of hemopoietic colony-stimulating factors by astrocytes. Journal of Immunology, 144, 3816–3821.
Mana, P., Linares, D., Fordham, S., Staykova, M., & Willenborg, D. (2006). Deleterious role of IFNgamma in a toxic model of central nervous system demyelination. American Journal of Pathology, 168, 1464–1473.PubMedCrossRef
Manetti, R., Parronchi, P., Giudizi, M. G., Piccinni, M. P., Maggi, E., Trinchieri, G., et al. (1993). Natural killer cell stimulatory factor (interleukin 12 [IL-12]) induces T helper type 1 (Th1)-specific immune responses and inhibits the development of IL-4-producing Th cells. Journal of Experimental Medicine, 177, 1199–1204.PubMedCrossRef
Mangan, P. R., Harrington, L. E., O’Quinn, D. B., Helms, W. S., Bullard, D. C., Elson, C. O., et al. (2006). Transforming growth factor-beta induces development of the T(H)17 lineage. Nature, 441, 231–234.PubMedCrossRef
Mannie, M. D., Abbott, D. J., & Blanchfield, J. L. (2009). Experimental autoimmune encephalomyelitis in Lewis rats: IFN-beta acts as a tolerogenic adjuvant for induction of neuroantigen-dependent tolerance. Journal of Immunology, 182, 5331–5341.CrossRef
Marik, C., Felts, P. A., Bauer, J., Lassmann, H., & Smith, K. J. (2007). Lesion genesis in a subset of patients with multiple sclerosis: A role for innate immunity? Brain, 130, 2800–2815.PubMedCrossRef
Markowitz, C. E. (2007). Interferon-beta: Mechanism of action and dosing issues. Neurology, 68, S8–S11.PubMedCrossRef
Marriott, M. P., Emery, B., Cate, H. S., Binder, M. D., Kemper, D., Wu, Q., et al. (2008). Leukemia inhibitory factor signaling modulates both central nervous system demyelination and myelin repair. Glia, 56, 686–698.PubMedCrossRef
Martin, D., Near, S. L., Bendele, A., & Russell, D. A. (1995). Inhibition of tumor necrosis factor is protective against neurologic dysfunction after active immunization of Lewis rats with myelin basic protein. Experimental Neurology, 131, 221–228.PubMedCrossRef
Marusic, S., Miyashiro, J. S., Douhan, J., 3rd, Konz, R. F., Xuan, D., Pelker, J. W., et al. (2002). Local delivery of granulocyte macrophage colony-stimulating factor by retrovirally transduced antigen-specific T cells leads to severe, chronic experimental autoimmune encephalomyelitis in mice. Neuroscience Letters, 332, 185–189.PubMedCrossRef
Mason, J. L., Suzuki, K., Chaplin, D. D., & Matsushima, G. K. (2001). Interleukin-1beta promotes repair of the CNS. Journal of Neuroscience, 21, 7046–7052.PubMed
Mason, J. L., Xuan, S., Dragatsis, I., Efstratiadis, A., & Goldman, J. E. (2003). Insulin-like growth factor (IGF) signaling through type 1 IGF receptor plays an important role in remyelination. Journal of Neuroscience, 23, 7710–7718.PubMed
Matthews, A. E., Weiss, S. R., & Paterson, Y. (2002). Murine hepatitis virus—A model for virus-induced CNS demyelination. Journal of Neurovirology, 8, 76–85.PubMedCrossRef
McGuinness, M. C., Powers, J. M., Bias, W. B., Schmeckpeper, B. J., Segal, A. H., Gowda, V. C., et al. (1997). Human leukocyte antigens and cytokine expression in cerebral inflammatory demyelinative lesions of X-linked adrenoleukodystrophy and multiple sclerosis. Journal of Neuroimmunology, 75, 174–182.PubMedCrossRef
McMahan, C. J., Slack, J. L., Mosley, B., Cosman, D., Lupton, S. D., Brunton, L. L., et al. (1991). A novel IL-1 receptor, cloned from B cells by mammalian expression, is expressed in many cell types. EMBO Journal, 10, 2821–2832.PubMed
McMahon, E. J., Bailey, S. L., Castenada, C. V., Waldner, H., & Miller, S. D. (2005). Epitope spreading initiates in the CNS in two mouse models of multiple sclerosis. Nature Medicine, 11, 335–339.PubMedCrossRef
McMahon, E. J., Suzuki, K., & Matsushima, G. K. (2002). Peripheral macrophage recruitment in cuprizone-induced CNS demyelination despite an intact blood-brain barrier. Journal of Neuroimmunology, 130, 32–45.PubMedCrossRef
McQualter, J. L., Darwiche, R., Ewing, C., Onuki, M., Kay, T. W., Hamilton, J. A., et al. (2001). Granulocyte macrophage colony-stimulating factor: A new putative therapeutic target in multiple sclerosis. Journal of Experimental Medicine, 194, 873–882.PubMedCrossRef
Melaragno, M. G., Cavet, M. E., Yan, C., Tai, L. K., Jin, Z. G., Haendeler, J., et al. (2004). Gas6 inhibits apoptosis in vascular smooth muscle: Role of Axl kinase and Akt. Journal of Molecular and Cellular Cardiology, 37, 881–887.PubMedCrossRef
Merrill, J. E. (1991). Effects of interleukin-1 and tumor necrosis factor-alpha on astrocytes, microglia, oligodendrocytes, and glial precursors in vitro. Developmental Neuroscience, 13, 130–137.PubMedCrossRef
Miller, A., Lider, O., Roberts, A. B., Sporn, M. B., & Weiner, H. L. (1992). Suppressor T cells generated by oral tolerization to myelin basic protein suppress both in vitro and in vivo immune responses by the release of transforming growth factor beta after antigen-specific triggering. Proceedings of the National Academy of Sciences of the United States of America, 89, 421–425.PubMedCrossRef
Miller, S. D., Vanderlugt, C. L., Begolka, W. S., Pao, W., Yauch, R. L., Neville, K. L., et al. (1997). Persistent infection with Theiler’s virus leads to CNS autoimmunity via epitope spreading. Nature Medicine, 3, 1133–1136.PubMedCrossRef
Mirshafiey, A., & Mohsenzadegan, M. (2009). TGF-beta as a promising option in the treatment of multiple sclerosis. Neuropharmacology, 56, 929–936.PubMedCrossRef
Mitrasinovic, O. M., Perez, G. V., Zhao, F., Lee, Y. L., Poon, C., & Murphy, G. M., Jr. (2001). Overexpression of macrophage colony-stimulating factor receptor on microglial cells induces an inflammatory response. Journal of Biological Chemistry, 276, 30142–30149.PubMedCrossRef
Mitrasinovic, O. M., Vincent, V. A., Simsek, D., & Murphy, G. M., Jr. (2003). Macrophage colony stimulating factor promotes phagocytosis by murine microglia. Neuroscience Letters, 344, 185–188.PubMedCrossRef
Miyanishi, M., Tada, K., Koike, M., Uchiyama, Y., Kitamura, T., & Nagata, S. (2007). Identification of Tim4 as a phosphatidylserine receptor. Nature, 450, 435–439.PubMedCrossRef
Mizuno, T., Sawada, M., Marunouchi, T., & Suzumura, A. (1994). Production of interleukin-10 by mouse glial cells in culture. Biochemical and Biophysical Research Communications, 205, 1907–1915.PubMedCrossRef
Mondal, S., Roy, A., & Pahan, K. (2009). Functional blocking monoclonal antibodies against IL-12p40 homodimer inhibit adoptive transfer of experimental allergic encephalomyelitis. Journal of Immunology, 182, 5013–5023.CrossRef
Moore, K. W., de Waal Malefyt, R., Coffman, R. L., & O’Garra, A. (2001). Interleukin-10 and the interleukin-10 receptor. Annual Review of Immunology, 19, 683–765.PubMedCrossRef
Morell, P., Barrett, C. V., Mason, J. L., Toews, A. D., Hostettler, J. D., Knapp, G. W., et al. (1998). Gene expression in brain during cuprizone-induced demyelination and remyelination. Molecular and Cellular Neurosciences, 12, 220–227.PubMedCrossRef
Morishima, N., Mizoguchi, I., Takeda, K., Mizuguchi, J., & Yoshimoto, T. (2009). TGF-beta is necessary for induction of IL-23R and Th17 differentiation by IL-6 and IL-23. Biochemical and Biophysical Research Communications, 386, 105–110.PubMedCrossRef
Mosmann, T. R., & Coffman, R. L. (1989). TH1 and TH2 cells: Different patterns of lymphokine secretion lead to different functional properties. Annual Review of Immunology, 7, 145–173.PubMedCrossRef
Mosser, D. M., & Zhang, X. (2008). Interleukin-10: New perspectives on an old cytokine. Immunological Reviews, 226, 205–218.PubMedCrossRef
MS/MRI Analysis Group. (1999). TNF neutralization in MS: Results of a randomized, placebo-controlled multicenter study. The Lenercept Multiple Sclerosis Study Group and The University of British Columbia MS/MRI Analysis Group. Neurology, 53, 457–465.
Mujtaba, M. G., Flowers, L. O., Patel, C. B., Patel, R. A., Haider, M. I., & Johnson, H. M. (2005). Treatment of mice with the suppressor of cytokine signaling-1 mimetic peptide, tyrosine kinase inhibitor peptide, prevents development of the acute form of experimental allergic encephalomyelitis and induces stable remission in the chronic. Journal of Immunology, 175, 5077–5086.
Murray, P. J. (2006). Understanding and exploiting the endogenous interleukin-10/STAT3-mediated anti-inflammatory response. Current Opinion in Pharmacology, 6, 379–386.PubMedCrossRef
Nakamura, Y. (2002). Regulating factors for microglial activation. Biological and Pharmaceutical Bulletin, 25, 945–953.PubMedCrossRef
Nakano, T., Ishimoto, Y., Kishino, J., Umeda, M., Inoue, K., Nagata, K., et al. (1997). Cell adhesion to phosphatidylserine mediated by a product of growth arrest-specific gene 6. Journal of Biological Chemistry, 272, 29411–29414.PubMedCrossRef
Nakayama, T., & Yamashita, M. (2008). Initiation and maintenance of Th2 cell identity. Current Opinion in Immunology, 20, 265–271.PubMedCrossRef
Navikas, V., Matusevicius, D., Soderstrom, M., Fredrikson, S., Kivisakk, P., Ljungdahl, A., et al. (1996). Increased interleukin-6 mRNA expression in blood and cerebrospinal fluid mononuclear cells in multiple sclerosis. Journal of Neuroimmunology, 64, 63–69.PubMedCrossRef
Neumann, H., Kotter, M. R., & Franklin, R. J. (2009). Debris clearance by microglia: An essential link between degeneration and regeneration. Brain, 132, 288–295.PubMedCrossRef
Nguyen, V. T., & Benveniste, E. N. (2000). IL-4-activated STAT-6 inhibits IFN-gamma-induced CD40 gene expression in macrophages/microglia. Journal of Immunology, 165, 6235–6243.
Nicoletti, F., Di Marco, R., Patti, F., Reggio, E., Nicoletti, A., Zaccone, P., et al. (1998). Blood levels of transforming growth factor-beta 1 (TGF-beta1) are elevated in both relapsing remitting and chronic progressive multiple sclerosis (MS) patients and are further augmented by treatment with interferon-beta 1b (IFN-beta1b). Clinical and Experimental Immunology, 113, 96–99.PubMedCrossRef
Nishiyama, A., Yu, M., Drazba, J. A., & Tuohy, V. K. (1997). Normal and reactive NG2 + glial cells are distinct from resting and activated microglia. Journal of Neuroscience Research, 48, 299–312.PubMedCrossRef
Nowak, E. C., Weaver, C. T., Turner, H., Begum-Haque, S., Becher, B., Schreiner, B., et al. (2009). IL-9 as a mediator of Th17-driven inflammatory disease. Journal of Experimental Medicine, 206, 1653–1660.PubMedCrossRef
O’Brien, K., Fitzgerald, D. C., Naiken, K., Alugupalli, K. R., Rostami, A. M., & Gran, B. (2008). Role of the innate immune system in autoimmune inflammatory demyelination. Current Medicinal Chemistry, 15, 1105–1115.PubMedCrossRef
O’Connor, R. A., Prendergast, C. T., Sabatos, C. A., Lau, C. W., Leech, M. D., Wraith, D. C., et al. (2008). Cutting edge: Th1 cells facilitate the entry of Th17 cells to the central nervous system during experimental autoimmune encephalomyelitis. Journal of Immunology, 181, 3750–3754.
O’Garra, A., & Arai, N. (2000). The molecular basis of T helper 1 and T helper 2 cell differentiation. Trends in Cell Biology, 10, 542–550.PubMedCrossRef
O’Keefe, G. M., Nguyen, V. T., & Benveniste, E. N. (1999). Class II transactivator and class II MHC gene expression in microglia: Modulation by the cytokines TGF-beta, IL-4, IL-13 and IL-10. European Journal of Immunology, 29, 1275–1285.PubMedCrossRef
O’Keefe, G. M., Nguyen, V. T., & Benveniste, E. N. (2002). Regulation and function of class II major histocompatibility complex, CD40, and B7 expression in macrophages and microglia: Implications in neurological diseases. Journal of Neurovirology, 8, 496–512.PubMedCrossRef
O’Keefe, G. M., Nguyen, V. T., Ping Tang, L. L., & Benveniste, E. N. (2001). IFN-gamma regulation of class II transactivator promoter IV in macrophages and microglia: Involvement of the suppressors of cytokine signaling-1 protein. Journal of Immunology, 166, 2260–2269.
O’Neill, L. A., & Greene, C. (1998). Signal transduction pathways activated by the IL-1 receptor family: Ancient signaling machinery in mammals, insects, and plants. Journal of Leukocyte Biology, 63, 650–657.PubMed
O’Shea, J. J., Ma, A., & Lipsky, P. (2002). Cytokines and autoimmunity. Nature Reviews Immunology, 2, 37–45.PubMedCrossRef
Okuda, Y., Sakoda, S., Bernard, C. C., Fujimura, H., Saeki, Y., Kishimoto, T., et al. (1998). IL-6-deficient mice are resistant to the induction of experimental autoimmune encephalomyelitis provoked by myelin oligodendrocyte glycoprotein. International Immunology, 10, 703–708.PubMedCrossRef
Okuda, Y., Sakoda, S., Fujimura, H., Saeki, Y., Kishimoto, T., & Yanagihara, T. (1999). IL-6 plays a crucial role in the induction phase of myelin oligodendrocyte glucoprotein 35–55 induced experimental autoimmune encephalomyelitis. Journal of Neuroimmunology, 101, 188–196.PubMedCrossRef
Oleszak, E. L., Chang, J. R., Friedman, H., Katsetos, C. D., & Platsoucas, C. D. (2004). Theiler’s virus infection: A model for multiple sclerosis. Clinical Microbiology Reviews, 17, 174–207.PubMedCrossRef
Pace, L., Rizzo, S., Palombi, C., Brombacher, F., & Doria, G. (2006). Cutting edge: IL-4-induced protection of CD4 + CD25- Th cells from CD4 + CD25 + regulatory T cell-mediated suppression. Journal of Immunology, 176, 3900–3904.
Pahan, K., Sheikh, F. G., Liu, X., Hilger, S., McKinney, M., & Petro, T. M. (2001). Induction of nitric-oxide synthase and activation of NF-kappaB by interleukin-12 p40 in microglial cells. Journal of Biological Chemistry, 276, 7899–7905.PubMedCrossRef
Panitch, H. S., Hirsch, R. L., Haley, A. S., & Johnson, K. P. (1987). Exacerbations of multiple sclerosis in patients treated with gamma interferon. Lancet, 1, 893–895.PubMedCrossRef
Parham, C., Chirica, M., Timans, J., Vaisberg, E., Travis, M., Cheung, J., et al. (2002). A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R. Journal of Immunology, 168, 5699–5708.
Pasquini, L. A., Calatayud, C. A., Bertone Una, A. L., Millet, V., Pasquini, J. M., & Soto, E. F. (2007). The neurotoxic effect of cuprizone on oligodendrocytes depends on the presence of pro-inflammatory cytokines secreted by microglia. Neurochemical Research, 32, 279–292.PubMedCrossRef
Patani, R., Balaratnam, M., Vora, A., & Reynolds, R. (2007). Remyelination can be extensive in multiple sclerosis despite a long disease course. Neuropathology and Applied Neurobiology, 33, 277–287.PubMedCrossRef
Patrikios, P., Stadelmann, C., Kutzelnigg, A., Rauschka, H., Schmidbauer, M., Laursen, H., et al. (2006). Remyelination is extensive in a subset of multiple sclerosis patients. Brain, 129, 3165–3172.PubMedCrossRef
Paty, D. W., & Li, D. K. (1993). Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. II. MRI analysis results of a multicenter, randomized, double-blind, placebo-controlled trial. UBC MS/MRI Study Group and the IFNB Multiple Sclerosis Study Group. Neurology, 43, 662–667.PubMed
Pender, M. P. (1999). Activation-induced apoptosis of autoreactive and alloreactive T lymphocytes in the target organ as a major mechanism of tolerance. Immunology and Cell Biology, 77, 216–223.PubMedCrossRef
Pender, M. P., Nguyen, K. B., McCombe, P. A., & Kerr, J. F. (1991). Apoptosis in the nervous system in experimental allergic encephalomyelitis. Journal of the Neurological Sciences, 104, 81–87.PubMedCrossRef
Pestka, S., Krause, C. D., & Walter, M. R. (2004). Interferons, interferon-like cytokines, and their receptors. Immunological Reviews, 202, 8–32.PubMedCrossRef
Peterson, J. W., Bo, L., Mork, S., Chang, A., Ransohoff, R. M., & Trapp, B. D. (2002). VCAM-1-positive microglia target oligodendrocytes at the border of multiple sclerosis lesions. Journal of Neuropathology and Experimental Neurology, 61, 539–546.PubMed
Pfeffer, K., Matsuyama, T., Kundig, T. M., Wakeham, A., Kishihara, K., Shahinian, A., et al. (1993). Mice deficient for the 55 kd tumor necrosis factor receptor are resistant to endotoxic shock, yet succumb to L. monocytogenes infection. Cell, 73, 457–467.PubMedCrossRef
Piccio, L., Buonsanti, C., Mariani, M., Cella, M., Gilfillan, S., Cross, A. H., et al. (2007). Blockade of TREM-2 exacerbates experimental autoimmune encephalomyelitis. European Journal of Immunology, 37, 1290–1301.PubMedCrossRef
Piccirillo, C. A., & Thornton, A. M. (2004). Cornerstone of peripheral tolerance: Naturally occurring CD4+CD25+ regulatory T cells. Trends in Immunology, 25, 374–380.PubMedCrossRef
Platten, M., Ho, P. P., Youssef, S., Fontoura, P., Garren, H., Hur, E. M., et al. (2005). Treatment of autoimmune neuroinflammation with a synthetic tryptophan metabolite. Science, 310, 850–855.PubMedCrossRef
Ponomarev, E. D., Maresz, K., Tan, Y., & Dittel, B. N. (2007a). CNS-derived interleukin-4 is essential for the regulation of autoimmune inflammation and induces a state of alternative activation in microglial cells. Journal of Neuroscience, 27, 10714–10721.PubMedCrossRef
Ponomarev, E. D., Shriver, L. P., Maresz, K., Pedras-Vasconcelos, J., Verthelyi, D., & Dittel, B. N. (2007b). GM-CSF production by autoreactive T cells is required for the activation of microglial cells and the onset of experimental autoimmune encephalomyelitis. Journal of Immunology, 178, 39–48.
Popko, B., & Baerwald, K. D. (1999). Oligodendroglial response to the immune cytokine interferon gamma. Neurochemical Research, 24, 331–338.PubMedCrossRef
Popovic, N., Schubart, A., Goetz, B. D., Zhang, S. C., Linington, C., & Duncan, I. D. (2002). Inhibition of autoimmune encephalomyelitis by a tetracycline. Annals of Neurology, 51, 215–223.PubMedCrossRef
Prineas, J. W., Barnard, R. O., Kwon, E. E., Sharer, L. R., & Cho, E. S. (1993). Multiple sclerosis: Remyelination of nascent lesions. Annals of Neurology, 33, 137–151.PubMedCrossRef
Prineas, J. W., & Graham, J. S. (1981). Multiple sclerosis: Capping of surface immunoglobulin G on macrophages engaged in myelin breakdown. Annals of Neurology, 10, 149–158.PubMedCrossRef
Prineas, J. W., Kwon, E. E., Goldenberg, P. Z., Ilyas, A. A., Quarles, R. H., Benjamins, J. A., et al. (1989). Multiple sclerosis. Oligodendrocyte proliferation and differentiation in fresh lesions. Laboratory Investigation, 61, 489–503.PubMed
Prinz, M., Schmidt, H., Mildner, A., Knobeloch, K. P., Hanisch, U. K., Raasch, J., et al. (2008). Distinct and nonredundant in vivo functions of IFNAR on myeloid cells limit autoimmunity in the central nervous system. Immunity, 28, 675–686.PubMedCrossRef
Pullen, L. C., Park, S. H., Miller, S. D., Dal Canto, M. C., & Kim, B. S. (1995). Treatment with bacterial LPS renders genetically resistant C57BL/6 mice susceptible to Theiler’s virus-induced demyelinating disease. Journal of Immunology, 155, 4497–4503.
Qian, L., Wei, S. J., Zhang, D., Hu, X., Xu, Z., Wilson, B., et al. (2008). Potent anti-inflammatory and neuroprotective effects of TGF-beta1 are mediated through the inhibition of ERK and p47phox-Ser345 phosphorylation and translocation in microglia. Journal of Immunology, 181, 660–668.
Qin, H., Roberts, K. L., Niyongere, S. A., Cong, Y., Elson, C. O., & Benveniste, E. N. (2007). Molecular mechanism of lipopolysaccharide-induced SOCS-3 gene expression in macrophages and microglia. Journal of Immunology, 179, 5966–5976.
Qin, H., Wilson, C. A., Lee, S. J., & Benveniste, E. N. (2006a). IFN-beta-induced SOCS-1 negatively regulates CD40 gene expression in macrophages and microglia. The FASEB Journal, 20, 985–987.PubMedCrossRef
Qin, H., Wilson, C. A., Roberts, K. L., Baker, B. J., Zhao, X., & Benveniste, E. N. (2006b). IL-10 inhibits lipopolysaccharide-induced CD40 gene expression through induction of suppressor of cytokine signaling-3. Journal of Immunology, 177, 7761–7771.
Quintana, A., Muller, M., Frausto, R. F., Ramos, R., Getts, D. R., Sanz, E., et al. (2009). Site-specific production of IL-6 in the central nervous system retargets and enhances the inflammatory response in experimental autoimmune encephalomyelitis. Journal of Immunology, 183, 2079–2088.CrossRef
Racke, M. K., Bonomo, A., Scott, D. E., Cannella, B., Levine, A., Raine, C. S., et al. (1994). Cytokine-induced immune deviation as a therapy for inflammatory autoimmune disease. Journal of Experimental Medicine, 180, 1961–1966.PubMedCrossRef
Racke, M. K., Dhib-Jalbut, S., Cannella, B., Albert, P. S., Raine, C. S., & McFarlin, D. E. (1991). Prevention and treatment of chronic relapsing experimental allergic encephalomyelitis by transforming growth factor-beta 1. Journal of Immunology, 146, 3012–3017.
Radu, D. L., Noben-Trauth, N., Hu-Li, J., Paul, W. E., & Bona, C. A. (2000). A targeted mutation in the IL-4Ralpha gene protects mice against autoimmune diabetes. Proceedings of the National Academy of Sciences of the United States of America, 97, 12700–12704.PubMedCrossRef
Raine, C. S., & Wu, E. (1993). Multiple sclerosis: Remyelination in acute lesions. Journal of Neuropathology and Experimental Neurology, 52, 199–204.PubMedCrossRef
Ransohoff, R. M., & Perry, V. H. (2009). Microglial physiology: Unique stimuli, specialized responses. Annual Review of Immunology, 27, 119–145.PubMedCrossRef
Re, F., Belyanskaya, S. L., Riese, R. J., Cipriani, B., Fischer, F. R., Granucci, F., et al. (2002). Granulocyte-macrophage colony-stimulating factor induces an expression program in neonatal microglia that primes them for antigen presentation. Journal of Immunology, 169, 2264–2273.
Rentzos, M., Nikolaou, C., Rombos, A., Voumvourakis, K., Segditsa, I., & Papageorgiou, C. (1996). Tumour necrosis factor alpha is elevated in serum and cerebrospinal fluid in multiple sclerosis and inflammatory neuropathies. Journal of Neurology, 243, 165–170.PubMedCrossRef
Rieckmann, P., Albrecht, M., Kitze, B., Weber, T., Tumani, H., Broocks, A., et al. (1995). Tumor necrosis factor-alpha messenger RNA expression in patients with relapsing-remitting multiple sclerosis is associated with disease activity. Annals of Neurology, 37, 82–88.PubMedCrossRef
Rothe, J., Lesslauer, W., Lotscher, H., Lang, Y., Koebel, P., Kontgen, F., et al. (1993). Mice lacking the tumour necrosis factor receptor 1 are resistant to TNF-mediated toxicity but highly susceptible to infection by Listeria monocytogenes. Nature, 364, 798–802.PubMedCrossRef
Rothlin, C. V., Ghosh, S., Zuniga, E. I., Oldstone, M. B., & Lemke, G. (2007). TAM receptors are pleiotropic inhibitors of the innate immune response. Cell, 131, 1124–1136.PubMedCrossRef
Rothuizen, L. E., Buclin, T., Spertini, F., Trinchard, I., Munafo, A., Buchwalder, P. A., et al. (1999). Influence of interferon beta-1a dose frequency on PBMC cytokine secretion and biological effect markers. Journal of Neuroimmunology, 99, 131–141.PubMedCrossRef
Rothwell, N. J., & Luheshi, G. N. (2000). Interleukin 1 in the brain: Biology, pathology and therapeutic target. Trends in Neurosciences, 23, 618–625.PubMedCrossRef
Ruddle, N. H., Bergman, C. M., McGrath, K. M., Lingenheld, E. G., Grunnet, M. L., Padula, S. J., et al. (1990). An antibody to lymphotoxin and tumor necrosis factor prevents transfer of experimental allergic encephalomyelitis. Journal of Experimental Medicine, 172, 1193–1200.PubMedCrossRef
Ruuls, S. R., de Labie, M. C., Weber, K. S., Botman, C. A., Groenestein, R. J., Dijkstra, C. D., et al. (1996). The length of treatment determines whether IFN-beta prevents or aggravates experimental autoimmune encephalomyelitis in Lewis rats. Journal of Immunology, 157, 5721–5731.
Samoilova, E. B., Horton, J. L., Hilliard, B., Liu, T. S., & Chen, Y. (1998). IL-6-deficient mice are resistant to experimental autoimmune encephalomyelitis: Roles of IL-6 in the activation and differentiation of autoreactive T cells. Journal of Immunology, 161, 6480–6486.
Santambrogio, L., Hochwald, G. M., Saxena, B., Leu, C. H., Martz, J. E., Carlino, J. A., et al. (1993). Studies on the mechanisms by which transforming growth factor-beta (TGF-beta) protects against allergic encephalomyelitis. Antagonism between TGF-beta and tumor necrosis factor. Journal of Immunology, 151, 1116–1127.
Sather, B. D., Treuting, P., Perdue, N., Miazgowicz, M., Fontenot, J. D., Rudensky, A. Y., et al. (2007). Altering the distribution of Foxp3(+) regulatory T cells results in tissue-specific inflammatory disease. Journal of Experimental Medicine, 204, 1335–1347.PubMedCrossRef
Schiffenbauer, J., Streit, W. J., Butfiloski, E., LaBow, M., Edwards, C., 3rd, & Moldawer, L. L. (2000). The induction of EAE is only partially dependent on TNF receptor signaling but requires the IL-1 type I receptor. Clinical Immunology, 95, 117–123.PubMedCrossRef
Schluesener, H. J., & Lider, O. (1989). Transforming growth factors beta 1 and beta 2: Cytokines with identical immunosuppressive effects and a potential role in the regulation of autoimmune T cell function. Journal of Neuroimmunology, 24, 249–258.PubMedCrossRef
Schmidt, H., Raasch, J., Merkler, D., Klinker, F., Krauss, S., Bruck, W., et al. (2009). Type I interferon receptor signalling is induced during demyelination while its function for myelin damage and repair is redundant. Experimental Neurology, 216, 306–311.PubMedCrossRef
Schmierer, B., & Hill, C. S. (2007). TGFbeta-SMAD signal transduction: Molecular specificity and functional flexibility. Nat Rev Mol Cell Biol, 8, 970–982.PubMedCrossRef
Schmitz, T., & Chew, L. J. (2008). Cytokines and myelination in the central nervous system. Scientific World Journal, 8, 1119–1147.PubMed
Schonrock, L. M., Gawlowski, G., & Bruck, W. (2000). Interleukin-6 expression in human multiple sclerosis lesions. Neuroscience Letters, 294, 45–48.PubMedCrossRef
Scolding, N., Franklin, R., Stevens, S., Heldin, C. H., Compston, A., & Newcombe, J. (1998). Oligodendrocyte progenitors are present in the normal adult human CNS and in the lesions of multiple sclerosis. Brain, 121(Pt 12), 2221–2228.PubMedCrossRef
Scutera, S., Fraone, T., Musso, T., Cappello, P., Rossi, S., Pierobon, D., et al. (2009). Survival and migration of human dendritic cells are regulated by an IFN-alpha-inducible Axl/Gas6 pathway. Journal of Immunology, 183, 3004–3013.CrossRef
Sebire, G., Emilie, D., Wallon, C., Hery, C., Devergne, O., Delfraissy, J. F., et al. (1993). In vitro production of IL-6, IL-1 beta, and tumor necrosis factor-alpha by human embryonic microglial and neural cells. Journal of Immunology, 150, 1517–1523.
Segal, B. M., Constantinescu, C. S., Raychaudhuri, A., Kim, L., Fidelus-Gort, R., & Kasper, L. H. (2008). Repeated subcutaneous injections of IL12/23 p40 neutralising antibody, ustekinumab, in patients with relapsing-remitting multiple sclerosis: A phase II, double-blind, placebo-controlled, randomised, dose-ranging study. Lancet Neurology, 7, 796–804.PubMedCrossRef
Segal, B. M., Dwyer, B. K., & Shevach, E. M. (1998). An interleukin (IL)-10/IL-12 immunoregulatory circuit controls susceptibility to autoimmune disease. Journal of Experimental Medicine, 187, 537–546.PubMedCrossRef
Selmaj, K. W., & Raine, C. S. (1988). Tumor necrosis factor mediates myelin and oligodendrocyte damage in vitro. Annals of Neurology, 23, 339–346.PubMedCrossRef
Selmaj, K. W., & Raine, C. S. (1995). Experimental autoimmune encephalomyelitis: Immunotherapy with anti-tumor necrosis factor antibodies and soluble tumor necrosis factor receptors. Neurology, 45, S44–S49.PubMed
Selmaj, K., Raine, C. S., & Cross, A. H. (1991). Anti-tumor necrosis factor therapy abrogates autoimmune demyelination. Annals of Neurology, 30, 694–700.PubMedCrossRef
Selvaraju, R., Bernasconi, L., Losberger, C., Graber, P., Kadi, L., Avellana-Adalid, V., et al. (2004). Osteopontin is upregulated during in vivo demyelination and remyelination and enhances myelin formation in vitro. Molecular and Cellular Neurosciences, 25, 707–721.PubMedCrossRef
Serada, S., Fujimoto, M., Mihara, M., Koike, N., Ohsugi, Y., Nomura, S., et al. (2008). IL-6 blockade inhibits the induction of myelin antigen-specific Th17 cells and Th1 cells in experimental autoimmune encephalomyelitis. Proceedings of the National Academy of Sciences of the United States of America, 105, 9041–9046.PubMedCrossRef
Setzu, A., Lathia, J. D., Zhao, C., Wells, K., Rao, M. S., Ffrench-Constant, C., et al. (2006). Inflammation stimulates myelination by transplanted oligodendrocyte precursor cells. Glia, 54, 297–303.PubMedCrossRef
Shankar, S. L., O’Guin, K., Cammer, M., McMorris, F. A., Stitt, T. N., Basch, R. S., et al. (2003). The growth arrest-specific gene product Gas6 promotes the survival of human oligodendrocytes via a phosphatidylinositol 3-kinase-dependent pathway. Journal of Neuroscience, 23, 4208–4218.PubMed
Shankar, S. L., O’Guin, K., Kim, M., Varnum, B., Lemke, G., Brosnan, C. F., et al. (2006). Gas6/Axl signaling activates the phosphatidylinositol 3-kinase/Akt1 survival pathway to protect oligodendrocytes from tumor necrosis factor alpha-induced apoptosis. Journal of Neuroscience, 26, 5638–5648.PubMedCrossRef
Sharif, M. N., Sosic, D., Rothlin, C. V., Kelly, E., Lemke, G., Olson, E. N., et al. (2006). Twist mediates suppression of inflammation by type I IFNs and Axl. Journal of Experimental Medicine, 203, 1891–1901.PubMedCrossRef
Shaw, M. K., Lorens, J. B., Dhawan, A., DalCanto, R., Tse, H. Y., Tran, A. B., et al. (1997). Local delivery of interleukin 4 by retrovirus-transduced T lymphocytes ameliorates experimental autoimmune encephalomyelitis. Journal of Experimental Medicine, 185, 1711–1714.PubMedCrossRef
Sheehan, K. C., Pinckard, J. K., Arthur, C. D., Dehner, L. P., Goeddel, D. V., & Schreiber, R. D. (1995). Monoclonal antibodies specific for murine p55 and p75 tumor necrosis factor receptors: Identification of a novel in vivo role for p75. Journal of Experimental Medicine, 181, 607–617.PubMedCrossRef
Shevach, E. M. (2000). Regulatory T cells in autoimmmunity. Annual Review of Immunology, 18, 423–449.PubMedCrossRef
Shields, S., Gilson, J., Blakemore, W., & Franklin, R. (2000). Remyelination occurs as extensively but more slowly in old rats compared to young rats following fliotoxin-induced CNS demyelination. Glia, 29, 102.PubMedCrossRef
Shinohara, M. L., Kim, J. H., Garcia, V. A., & Cantor, H. (2008). Engagement of the type I interferon receptor on dendritic cells inhibits T helper 17 cell development: Role of intracellular osteopontin. Immunity, 29, 68–78.PubMedCrossRef
Shull, M. M., Ormsby, I., Kier, A. B., Pawlowski, S., Diebold, R. J., Yin, M., et al. (1992). Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease. Nature, 359, 693–699.PubMedCrossRef
Smith, M. E. (1999). Phagocytosis of myelin in demyelinative disease: A review. Neurochemical Research, 24, 261–268.PubMedCrossRef
Smith, M. E., van der Maesen, K., & Somera, F. P. (1998). Macrophage and microglial responses to cytokines in vitro: Phagocytic activity, proteolytic enzyme release, and free radical production. Journal of Neuroscience Research, 54, 68–78.PubMedCrossRef
Soh, J., Donnelly, R. J., Kotenko, S., Mariano, T. M., Cook, J. R., Wang, N., et al. (1994). Identification and sequence of an accessory factor required for activation of the human interferon gamma receptor. Cell, 76, 793–802.PubMedCrossRef
Soldan, S. S., Alvarez Retuerto, A. I., Sicotte, N. L., & Voskuhl, R. R. (2004). Dysregulation of IL-10 and IL-12p40 in secondary progressive multiple sclerosis. Journal of Neuroimmunology, 146, 209–215.PubMedCrossRef
Sonobe, Y., Liang, J., Jin, S., Zhang, G., Takeuchi, H., Mizuno, T., et al. (2008). Microglia express a functional receptor for interleukin-23. Biochemical and Biophysical Research Communications, 370, 129–133.PubMedCrossRef
Sonobe, Y., Yawata, I., Kawanokuchi, J., Takeuchi, H., Mizuno, T., & Suzumura, A. (2005). Production of IL-27 and other IL-12 family cytokines by microglia and their subpopulations. Brain Research, 1040, 202–207.PubMedCrossRef
Sospedra, M., & Martin, R. (2005). Immunology of multiple sclerosis. Annual Review of Immunology, 23, 683–747.PubMedCrossRef
Staykova, M. A., Berven, L. A., Cowden, W. B., Willenborg, D. O., & Crouch, M. F. (2003). Nitric oxide induces polarization of actin in encephalitogenic T cells and inhibits their in vitro trans-endothelial migration in a p70S6 kinase-independent manner. The FASEB Journal, 17, 1337–1339.PubMed
Steinman, L., & Zamvil, S. S. (2005). Virtues and pitfalls of EAE for the development of therapies for multiple sclerosis. Trends in Immunology, 26, 565–571.PubMedCrossRef
Stevens, D. B., Gould, K. E., & Swanborg, R. H. (1994). Transforming growth factor-beta 1 inhibits tumor necrosis factor-alpha/lymphotoxin production and adoptive transfer of disease by effector cells of autoimmune encephalomyelitis. Journal of Neuroimmunology, 51, 77–83.PubMedCrossRef
Stumhofer, J. S., Laurence, A., Wilson, E. H., Huang, E., Tato, C. M., Johnson, L. M., et al. (2006). Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the central nervous system. Nature Immunology, 7, 937–945.PubMedCrossRef
Sugiura, S., Lahav, R., Han, J., Kou, S. Y., Banner, L. R., de Pablo, F., et al. (2000). Leukaemia inhibitory factor is required for normal inflammatory responses to injury in the peripheral and central nervous systems in vivo and is chemotactic for macrophages in vitro. European Journal of Neuroscience, 12, 457–466.PubMedCrossRef
Suzumura, A., Sawada, M., Yamamoto, H., & Marunouchi, T. (1993). Transforming growth factor-beta suppresses activation and proliferation of microglia in vitro. Journal of Immunology, 151, 2150–2158.
Takahashi, K., Prinz, M., Stagi, M., Chechneva, O., & Neumann, H. (2007). TREM2-transduced myeloid precursors mediate nervous tissue debris clearance and facilitate recovery in an animal model of multiple sclerosis. PLoS Medicine, 4, e124.PubMedCrossRef
Takeda, A., Hamano, S., Yamanaka, A., Hanada, T., Ishibashi, T., Mak, T. W., et al. (2003). Cutting edge: Role of IL-27/WSX-1 signaling for induction of T-bet through activation of STAT1 during initial Th1 commitment. Journal of Immunology, 170, 4886–4890.
Takeuchi, A., Miyaishi, O., Kiuchi, K., & Isobe, K. (2001). Macrophage colony-stimulating factor is expressed in neuron and microglia after focal brain injury. Journal of Neuroscience Research, 65, 38–44.PubMedCrossRef
Taniguchi, T., & Takaoka, A. (2001). A weak signal for strong responses: Interferon-alpha/beta revisited. Nature Reviews. Molecular Cell Biology, 2, 378–386.PubMedCrossRef
Tansey, M. G., & Wyss-Coray, T. (2008). Cytokines in CNS Inflammation and Disease. In T. E. Lane, M. Carson, C. Bergman, & T. Wyss-Coray (Eds.), Central nervous system diseases and inflammation (pp. 59–106). Heidelberg: Springer.CrossRef
Tartaglia, L. A., Goeddel, D. V., Reynolds, C., Figari, I. S., Weber, R. F., Fendly, B. M., et al. (1993). Stimulation of human T-cell proliferation by specific activation of the 75-kDa tumor necrosis factor receptor. Journal of Immunology, 151, 4637–4641.
Teige, I., Liu, Y., & Issazadeh-Navikas, S. (2006). IFN-beta inhibits T cell activation capacity of central nervous system APCs. Journal of Immunology, 177, 3542–3553.
Teige, I., Treschow, A., Teige, A., Mattsson, R., Navikas, V., Leanderson, T., et al. (2003). IFN-beta gene deletion leads to augmented and chronic demyelinating experimental autoimmune encephalomyelitis. Journal of Immunology, 170, 4776–4784.
Tenorio, E., & Mack, D. M. (2008). Therapeutic anti-inflammatory mechanism of action of Type I interferons. Bioscience Hypotheses, 1, 218–222.CrossRef
Thakker, P., Leach, M. W., Kuang, W., Benoit, S. E., Leonard, J. P., & Marusic, S. (2007). IL-23 is critical in the induction but not in the effector phase of experimental autoimmune encephalomyelitis. Journal of Immunology, 178, 2589–2598.
‘t Hart, B. A., Brok, H. P., Remarque, E., Benson, J., Treacy, G., Amor, S., et al. (2005). Suppression of ongoing disease in a nonhuman primate model of multiple sclerosis by a human-anti-human IL-12p40 antibody. Journal of Immunology, 175, 4761–4768.
Theofilopoulos, A. N., Baccala, R., Beutler, B., & Kono, D. H. (2005). Type I interferons (alpha/beta) in immunity and autoimmunity. Annual Review of Immunology, 23, 307–336.PubMedCrossRef
Thomas, K. E., Galligan, C. L., Newman, R. D., Fish, E. N., & Vogel, S. N. (2006). Contribution of interferon-beta to the murine macrophage response to the toll-like receptor 4 agonist, lipopolysaccharide. Journal of Biological Chemistry, 281, 31119–31130.PubMedCrossRef
Toshchakov, V., Jones, B. W., Perera, P. Y., Thomas, K., Cody, M. J., Zhang, S., et al. (2002). TLR4, but not TLR2, mediates IFN-beta-induced STAT1alpha/beta-dependent gene expression in macrophages. Nature Immunology, 3, 392–398.PubMedCrossRef
Totoiu, M. O., Nistor, G. I., Lane, T. E., & Keirstead, H. S. (2004). Remyelination, axonal sparing, and locomotor recovery following transplantation of glial-committed progenitor cells into the MHV model of multiple sclerosis. Experimental Neurology, 187, 254–265.PubMedCrossRef
Tran, E. H., Prince, E. N., & Owens, T. (2000). IFN-gamma shapes immune invasion of the central nervous system via regulation of chemokines. Journal of Immunology, 164, 2759–2768.
Trapp, B. D., Peterson, J., Ransohoff, R. M., Rudick, R., Mork, S., & Bo, L. (1998). Axonal transection in the lesions of multiple sclerosis. New England Journal of Medicine, 338, 278–285.PubMedCrossRef
Trapp, B. D., Ransohoff, R., & Rudick, R. (1999). Axonal pathology in multiple sclerosis: Relationship to neurologic disability. Current Opinion in Neurology, 12, 295–302.PubMedCrossRef
Trebst, C., Heine, S., Lienenklaus, S., Lindner, M., Baumgartner, W., Weiss, S., et al. (2007). Lack of interferon-beta leads to accelerated remyelination in a toxic model of central nervous system demyelination. Acta Neuropathologica, 114, 587–596.PubMedCrossRef
Trinchieri, G. (2003). Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nature Reviews Immunology, 3, 133–146.PubMedCrossRef
Tsukada, N., Miyagi, K., Matsuda, M., Yanagisawa, N., & Yone, K. (1991). Tumor necrosis factor and interleukin-1 in the CSF and sera of patients with multiple sclerosis. Journal of the Neurological Sciences, 104, 230–234.PubMedCrossRef
Ulrich, R., Seeliger, F., Kreutzer, M., Germann, P. G., & Baumgärtner, W. (2008). Limited remyelination in Theiler’s murine encephalomyelitis due to insufficient oligodendroglial differentiation of nerve/glial antigen 2 (NG2)-positive putative oligodendroglial progenitor cells. Neuropathology and Applied Neurobiology, 34, 603–620.PubMedCrossRef
van Oosten, B. W., Barkhof, F., Truyen, L., Boringa, J. B., Bertelsmann, F. W., von Blomberg, B. M., et al. (1996). Increased MRI activity and immune activation in two multiple sclerosis patients treated with the monoclonal anti-tumor necrosis factor antibody cA2. Neurology, 47, 1531–1534.PubMed
Van Ostade, X., Vandenabeele, P., Everaerdt, B., Loetscher, H., Gentz, R., Brockhaus, M., et al. (1993). Human TNF mutants with selective activity on the p55 receptor. Nature, 361, 266–269.PubMedCrossRef
Vandenabeele, P., Declercq, W., Beyaert, R., & Fiers, W. (1995). Two tumour necrosis factor receptors: Structure and function. Trends in Cell Biology, 5, 392–399.PubMedCrossRef
Vargas, M. E., & Barres, B. A. (2007). Why is Wallerian degeneration in the CNS so slow? Annual Review of Neuroscience, 30, 153–179.PubMedCrossRef
Vela, J. M., Molina-Holgado, E., Arevalo-Martin, A., Almazan, G., & Guaza, C. (2002). Interleukin-1 regulates proliferation and differentiation of oligodendrocyte progenitor cells. Molecular and Cellular Neurosciences, 20, 489–502.PubMedCrossRef
Veldhoen, M., Hocking, R. J., Flavell, R. A., & Stockinger, B. (2006). Signals mediated by transforming growth factor-beta initiate autoimmune encephalomyelitis, but chronic inflammation is needed to sustain disease. Nature Immunology, 7, 1151–1156.PubMedCrossRef
Villarroya, H., Violleau, K., Ben Younes-Chennoufi, A., & Baumann, N. (1996). Myelin-induced experimental allergic encephalomyelitis in Lewis rats: Tumor necrosis factor alpha levels in serum and cerebrospinal fluid immunohistochemical expression in glial cells and macrophages of optic nerve and spinal cord. Journal of Neuroimmunology, 64, 55–61.PubMedCrossRef
von Zahn, J., Moller, T., Kettenmann, H., & Nolte, C. (1997). Microglial phagocytosis is modulated by pro- and anti-inflammatory cytokines. Neuroreport, 8, 3851–3856.CrossRef
Waetzig, V., Czeloth, K., Hidding, U., Mielke, K., Kanzow, M., Brecht, S., et al. (2005). c-Jun N-terminal kinases (JNKs) mediate pro-inflammatory actions of microglia. Glia, 50, 235–246.PubMedCrossRef
Wahl, S. M. (1994). Transforming growth factor beta: The good, the bad, and the ugly. Journal of Experimental Medicine, 180, 1587–1590.PubMedCrossRef
Wahl, S. M., Hunt, D. A., Wakefield, L. M., McCartney-Francis, N., Wahl, L. M., Roberts, A. B., et al. (1987). Transforming growth factor type beta induces monocyte chemotaxis and growth factor production. Proceedings of the National Academy of Sciences of the United States of America, 84, 5788–5792.PubMedCrossRef
Wajant, H., Pfizenmaier, K., & Scheurich, P. (2003). Tumor necrosis factor signaling. Cell Death and Differentiation, 10, 45–65.PubMedCrossRef
Wallach, D., Varfolomeev, E. E., Malinin, N. L., Goltsev, Y. V., Kovalenko, A. V., & Boldin, M. P. (1999). Tumor necrosis factor receptor and Fas signaling mechanisms. Annual Review of Immunology, 17, 331–367.PubMedCrossRef
Wang, J., Asensio, V. C., & Campbell, I. L. (2002). Cytokines and chemokines as mediators of protection and injury in the central nervous system assessed in transgenic mice. Current Topics in Microbiology and Immunology, 265, 23–48.PubMed
Wang, Z., Hong, J., Sun, W., Xu, G., Li, N., Chen, X., et al. (2006). Role of IFN-gamma in induction of Foxp3 and conversion of CD4 + CD25- T cells to CD4 + Tregs. Journal of Clinical Investigation, 116, 2434–2441.PubMed
Wang, Y., Lawson, M. A., Dantzer, R., & Kelley, K. W. (2010). LPS-induced indoleamine 2, 3-dioxygenase is regulated in an interferon-gamma-independent manner by a JNK signaling pathway in primary murine microglia. Brain, Behavior, and Immunity, 24, 201–209.PubMedCrossRef
Wei, R., & Jonakait, G. M. (1999). Neurotrophins and the anti-inflammatory agents interleukin-4 (IL-4), IL-10, IL-11 and transforming growth factor-beta1 (TGF-beta1) down-regulate T cell costimulatory molecules B7 and CD40 on cultured rat microglia. Journal of Neuroimmunology, 95, 8–18.PubMedCrossRef
Weinger, J. G., Omari, K. M., Marsden, K., Raine, C. S., & Shafit-Zagardo, B. (2009). Up-regulation of soluble Axl and Mer receptor tyrosine kinases negatively correlates with Gas6 in established multiple sclerosis lesions. American Journal of Pathology, 175, 283–293.PubMedCrossRef
Weinstock-Guttman, B., Ramanathan, M., & Zivadinov, R. (2008). Interferon-beta treatment for relapsing multiple sclerosis. Expert Opinion on Biological Therapy, 8, 1435–1447.PubMedCrossRef
Wesche, H., Henzel, W. J., Shillinglaw, W., Li, S., & Cao, Z. (1997). MyD88: An adapter that recruits IRAK to the IL-1 receptor complex. Immunity, 7, 837–847.PubMedCrossRef
Wesemann, D. R., Dong, Y., O’Keefe, G. M., Nguyen, V. T., & Benveniste, E. N. (2002). Suppressor of cytokine signaling 1 inhibits cytokine induction of CD40 expression in macrophages. Journal of Immunology, 169, 2354–2360.
Williams, K., Dooley, N., Ulvestad, E., Becher, B., & Antel, J. P. (1996). IL-10 production by adult human derived microglial cells. Neurochemistry International, 29, 55–64.PubMedCrossRef
Windhagen, A., Newcombe, J., Dangond, F., Strand, C., Woodroofe, M. N., Cuzner, M. L., et al. (1995). Expression of costimulatory molecules B7-1 (CD80), B7-2 (CD86), and interleukin 12 cytokine in multiple sclerosis lesions. Journal of Experimental Medicine, 182, 1985–1996.PubMedCrossRef
Wirjatijasa, F., Dehghani, F., Blaheta, R. A., Korf, H. W., & Hailer, N. P. (2002). Interleukin-4, interleukin-10, and interleukin-1-receptor antagonist but not transforming growth factor-beta induce ramification and reduce adhesion molecule expression of rat microglial cells. Journal of Neuroscience Research, 68, 579–587.PubMedCrossRef
Wolf, S. F., Temple, P. A., Kobayashi, M., Young, D., Dicig, M., Lowe, L., et al. (1991). Cloning of cDNA for natural killer cell stimulatory factor, a heterodimeric cytokine with multiple biologic effects on T and natural killer cells. Journal of Immunology, 146, 3074–3081.
Wolswijk, G. (2002). Oligodendrocyte precursor cells in the demyelinated multiple sclerosis spinal cord. Brain, 125, 338–349.PubMedCrossRef
Xiao, B. G., Bai, X. F., Zhang, G. X., Hojeberg, B., & Link, H. (1996). Shift from anti- to proinflammatory cytokine profiles in microglia through LPS- or IFN-gamma-mediated pathways. Neuroreport, 7, 1893–1898.PubMedCrossRef
Xiao, B. G., Ma, C. G., Xu, L. Y., Link, H., & Lu, C. Z. (2008). IL-12/IFN-gamma/NO axis plays critical role in development of Th1-mediated experimental autoimmune encephalomyelitis. Molecular Immunology, 45, 1191–1196.PubMedCrossRef
Yadav, M. C., Burudi, E. M., Alirezaei, M., Flynn, C. C., Watry, D. D., Lanigan, C. M., et al. (2007). IFN-gamma-induced IDO and WRS expression in microglia is differentially regulated by IL-4. Glia, 55, 1385–1396.PubMedCrossRef
Yaguchi, M., Ohta, S., Toyama, Y., Kawakami, Y., & Toda, M. (2008). Functional recovery after spinal cord injury in mice through activation of microglia and dendritic cells after IL-12 administration. Journal of Neuroscience Research, 86, 1972–1980.PubMedCrossRef
Yamamoto, M., Sato, S., Hemmi, H., Hoshino, K., Kaisho, T., Sanjo, H., et al. (2003a). Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science, 301, 640–643.PubMedCrossRef
Yamamoto, M., Sato, S., Hemmi, H., Uematsu, S., Hoshino, K., Kaisho, T., et al. (2003b). TRAM is specifically involved in the Toll-like receptor 4-mediated MyD88-independent signaling pathway. Nature Immunology, 4, 1144–1150.PubMedCrossRef
Yan, H., & Rivkees, S. (2002). Hepatocyte growth factor stimulates the proliferation and migration of oligodendrocyte precursor cells. Journal of Neuroscience Research, 69, 597–606.PubMedCrossRef
Yoshimura, A. (2005). Negative regulation of cytokine signaling. Clinical Reviews in Allergy and Immunology, 28, 205–220.PubMedCrossRef
Young, D. A., Lowe, L. D., Booth, S. S., Whitters, M. J., Nicholson, L., Kuchroo, V. K., et al. (2000). IL-4, IL-10, IL-13, and TGF-beta from an altered peptide ligand-specific Th2 cell clone down-regulate adoptive transfer of experimental autoimmune encephalomyelitis. Journal of Immunology, 164, 3563–3572.
Yu, M., Nishiyama, A., Trapp, B. D., & Tuohy, V. K. (1996). Interferon-beta inhibits progression of relapsing-remitting experimental autoimmune encephalomyelitis. Journal of Neuroimmunology, 64, 91–100.PubMedCrossRef
Zhang, B., Harness, J., Somodevilla-Torres, M. J., Hillyard, N. C., Mould, A. W., Alewood, D., et al. (2000). Early pregnancy factor suppresses experimental autoimmune encephalomyelitis induced in Lewis rats with myelin basic protein and in SJL/J mice with myelin proteolipid protein peptide 139–151. Journal of the Neurological Sciences, 182, 5–15.PubMedCrossRef
Zhao, C., Fancy, S. P., ffrench-Constant, C., & Franklin, R. J. (2008). Osteopontin is extensively expressed by macrophages following CNS demyelination but has a redundant role in remyelination. Neurobiology of Diseases, 31, 209–217.CrossRef
Zhao, W., Xie, W., Xiao, Q., Beers, D. R., & Appel, S. H. (2006). Protective effects of an anti-inflammatory cytokine, interleukin-4, on motoneuron toxicity induced by activated microglia. Journal of Neurochemistry, 99, 1176–1187.PubMedCrossRef
Zheng, L., Fisher, G., Miller, R. E., Peschon, J., Lynch, D. H., & Lenardo, M. J. (1995). Induction of apoptosis in mature T cells by tumour necrosis factor. Nature, 377, 348–351.PubMedCrossRef
Metadata
Title
Role of Cytokines as Mediators and Regulators of Microglial Activity in Inflammatory Demyelination of the CNS
Authors
Tobias D. Merson
Michele D. Binder
Trevor J. Kilpatrick
Publication date
01-06-2010
Publisher
Humana Press Inc
Published in
NeuroMolecular Medicine / Issue 2/2010
Print ISSN: 1535-1084
Electronic ISSN: 1559-1174
DOI
https://doi.org/10.1007/s12017-010-8112-z

Other articles of this Issue 2/2010

NeuroMolecular Medicine 2/2010 Go to the issue

REVIEW PAPER

Phospholipases A2 and Inflammatory Responses in the Central Nervous System

Original Paper

The Role of the Complement System and the Activation Fragment C5a in the Central Nervous System

Review Paper

A Clear and Present Danger: Endogenous Ligands of Toll-like Receptors

Original Paper

Leukocyte Recruitment and Ischemic Brain Injury

Review Paper

Involvement of Fc Receptors in Disorders of the Central Nervous System