Skip to main content
Top
Published in: Clinical Reviews in Allergy & Immunology 1/2016

01-02-2016

Toll-Like Receptor Pathways in Autoimmune Diseases

Authors: Ji-Qing Chen, Peter Szodoray, Margit Zeher

Published in: Clinical Reviews in Allergy & Immunology | Issue 1/2016

Login to get access

Abstract

Autoimmune diseases are a family of chronic systemic inflammatory disorders, characterized by the dysregulation of the immune system which finally results in the break of tolerance to self-antigen. Several studies suggest that Toll-like receptors (TLRs) play an essential role in the pathogenesis of autoimmune diseases. TLRs belong to the family of pattern recognition receptors (PRRs) that recognize a wide range of pathogen-associated molecular patterns (PAMPs). TLRs are type I transmembrane proteins and located on various cellular membranes. Two main groups have been classified based on their location; the extracelluar group referred to the ones located on the plasma membrane while the intracellular group all located in endosomal compartments responsible for the recognition of nucleic acids. They are released by the host cells and trigger various intracellular pathways which results in the production of proinflammatory cytokines, chemokines, as well as the expression of co-stimulatory molecules to protect against invading microorganisms. In particular, TLR pathway-associated proteins, such as IRAK, TRAF, and SOCS, are often dysregulated in this group of diseases. TLR-associated gene expression profile analysis together with single nucleotide polymorphism (SNP) assessment could be important to explain the pathomechanism driving autoimmune diseases. In this review, we summarize recent findings on TLR pathway regulation in various autoimmune diseases, including Sjögren’s syndrome (SS), systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), systemic sclerosis (SSc), and psoriasis.
Literature
1.
go back to reference Amital H, Govoni M, Maya R et al (2008) Role of infectious agents in systemic rheumatic diseases. Clin Exp Rheumatol 26:S27–32PubMed Amital H, Govoni M, Maya R et al (2008) Role of infectious agents in systemic rheumatic diseases. Clin Exp Rheumatol 26:S27–32PubMed
8.
go back to reference Bowie A, O’Neill LA (2000) The interleukin-1 receptor/Toll-like receptor superfamily: signal generators for pro-inflammatory interleukins and microbial products. J Leukoc Biol 67:508–514PubMed Bowie A, O’Neill LA (2000) The interleukin-1 receptor/Toll-like receptor superfamily: signal generators for pro-inflammatory interleukins and microbial products. J Leukoc Biol 67:508–514PubMed
12.
go back to reference Yamamoto M, Sato S, Mori K et al (2002) Cutting edge: a novel Toll/IL-1 receptor domain-containing adapter that preferentially activates the IFN-beta promoter in the Toll-like receptor signaling. J Immunol 169:6668–6672PubMedCrossRef Yamamoto M, Sato S, Mori K et al (2002) Cutting edge: a novel Toll/IL-1 receptor domain-containing adapter that preferentially activates the IFN-beta promoter in the Toll-like receptor signaling. J Immunol 169:6668–6672PubMedCrossRef
20.
go back to reference Shimazu R, Akashi S, Ogata H et al (1999) MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4. J Exp Med 189:1777–1782PubMedCentralPubMedCrossRef Shimazu R, Akashi S, Ogata H et al (1999) MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4. J Exp Med 189:1777–1782PubMedCentralPubMedCrossRef
21.
go back to reference Kurt-Jones EA, Popova L, Kwinn L et al (2000) Pattern recognition receptors TLR4 and CD14 mediate response to respiratory syncytial virus. Nat Immunol 1:398–401. doi:10.1038/80833 PubMedCrossRef Kurt-Jones EA, Popova L, Kwinn L et al (2000) Pattern recognition receptors TLR4 and CD14 mediate response to respiratory syncytial virus. Nat Immunol 1:398–401. doi:10.​1038/​80833 PubMedCrossRef
22.
go back to reference Cao Z, Henzel WJ, Gao X (1996) IRAK: a kinase associated with the interleukin-1 receptor. Science 271:1128–1131PubMedCrossRef Cao Z, Henzel WJ, Gao X (1996) IRAK: a kinase associated with the interleukin-1 receptor. Science 271:1128–1131PubMedCrossRef
23.
go back to reference Janssens S, Beyaert R (2003) Functional diversity and regulation of different interleukin-1 receptor-associated kinase (IRAK) family members. Mol Cell 11:293–302PubMedCrossRef Janssens S, Beyaert R (2003) Functional diversity and regulation of different interleukin-1 receptor-associated kinase (IRAK) family members. Mol Cell 11:293–302PubMedCrossRef
26.
go back to reference Hsu H, Xiong J, Goeddel DV (1995) The TNF receptor 1-associated protein TRADD signals cell death and NF-kappa B activation. Cell 81:495–504PubMedCrossRef Hsu H, Xiong J, Goeddel DV (1995) The TNF receptor 1-associated protein TRADD signals cell death and NF-kappa B activation. Cell 81:495–504PubMedCrossRef
27.
go back to reference Youn J, Kim H-Y, Park JH et al (2002) Regulation of TNF-alpha-mediated hyperplasia through TNF receptors, TRAFs, and NF-kappaB in synoviocytes obtained from patients with rheumatoid arthritis. Immunol Lett 83:85–93PubMedCrossRef Youn J, Kim H-Y, Park JH et al (2002) Regulation of TNF-alpha-mediated hyperplasia through TNF receptors, TRAFs, and NF-kappaB in synoviocytes obtained from patients with rheumatoid arthritis. Immunol Lett 83:85–93PubMedCrossRef
28.
go back to reference Rothe M, Sarma V, Dixit VM, Goeddel DV (1995) TRAF2-mediated activation of NF-kappa B by TNF receptor 2 and CD40. Science 269:1424–1427PubMedCrossRef Rothe M, Sarma V, Dixit VM, Goeddel DV (1995) TRAF2-mediated activation of NF-kappa B by TNF receptor 2 and CD40. Science 269:1424–1427PubMedCrossRef
29.
go back to reference Ihnatko R, Kubes M (2007) TNF signaling: early events and phosphorylation. Gen Physiol Biophys 26:159–167PubMed Ihnatko R, Kubes M (2007) TNF signaling: early events and phosphorylation. Gen Physiol Biophys 26:159–167PubMed
31.
go back to reference Lee NK, Lee SY (2002) Modulation of life and death by the tumor necrosis factor receptor-associated factors (TRAFs). J Biochem Mol Biol 35:61–66PubMedCrossRef Lee NK, Lee SY (2002) Modulation of life and death by the tumor necrosis factor receptor-associated factors (TRAFs). J Biochem Mol Biol 35:61–66PubMedCrossRef
33.
go back to reference Wu H, Arron JR (2003) TRAF6, a molecular bridge spanning adaptive immunity, innate immunity and osteoimmunology. Bioessays News Rev Mol Cell Dev Biol 25:1096–1105. doi:10.1002/bies.10352 CrossRef Wu H, Arron JR (2003) TRAF6, a molecular bridge spanning adaptive immunity, innate immunity and osteoimmunology. Bioessays News Rev Mol Cell Dev Biol 25:1096–1105. doi:10.​1002/​bies.​10352 CrossRef
34.
go back to reference Naito A, Azuma S, Tanaka S et al (1999) Severe osteopetrosis, defective interleukin-1 signalling and lymph node organogenesis in TRAF6-deficient mice. Genes Cells Devoted Mol Cell Mech 4:353–362CrossRef Naito A, Azuma S, Tanaka S et al (1999) Severe osteopetrosis, defective interleukin-1 signalling and lymph node organogenesis in TRAF6-deficient mice. Genes Cells Devoted Mol Cell Mech 4:353–362CrossRef
39.
go back to reference Mansell A, Smith R, Doyle SL et al (2006) Suppressor of cytokine signaling 1 negatively regulates Toll-like receptor signaling by mediating Mal degradation. Nat Immunol 7:148–155. doi:10.1038/ni1299 PubMedCrossRef Mansell A, Smith R, Doyle SL et al (2006) Suppressor of cytokine signaling 1 negatively regulates Toll-like receptor signaling by mediating Mal degradation. Nat Immunol 7:148–155. doi:10.​1038/​ni1299 PubMedCrossRef
40.
go back to reference Zeher M, Szodoray P (2009) Sjögren’s syndrome and associated disorders. Transworld Research Network, Kerala Zeher M, Szodoray P (2009) Sjögren’s syndrome and associated disorders. Transworld Research Network, Kerala
44.
go back to reference Kawakami A, Nakashima K, Tamai M et al (2007) Toll-like receptor in salivary glands from patients with Sjögren’s syndrome: functional analysis by human salivary gland cell line. J Rheumatol 34:1019–1026PubMed Kawakami A, Nakashima K, Tamai M et al (2007) Toll-like receptor in salivary glands from patients with Sjögren’s syndrome: functional analysis by human salivary gland cell line. J Rheumatol 34:1019–1026PubMed
48.
go back to reference Szodoray P, Gal I, Barath S et al (2008) Immunological alterations in newly diagnosed primary Sjögren’s syndrome characterized by skewed peripheral T-cell subsets and inflammatory cytokines. Scand J Rheumatol 37:205–212. doi:10.1080/03009740801910361 PubMedCrossRef Szodoray P, Gal I, Barath S et al (2008) Immunological alterations in newly diagnosed primary Sjögren’s syndrome characterized by skewed peripheral T-cell subsets and inflammatory cytokines. Scand J Rheumatol 37:205–212. doi:10.​1080/​0300974080191036​1 PubMedCrossRef
49.
go back to reference Rothfield N (1989) Clinical aspects and treatment of systemic lupus erythematosus. Curr Opin Rheumatol 1:327–331PubMedCrossRef Rothfield N (1989) Clinical aspects and treatment of systemic lupus erythematosus. Curr Opin Rheumatol 1:327–331PubMedCrossRef
54.
go back to reference Bengtsson AA, Sturfelt G, Truedsson L et al (2000) Activation of type I interferon system in systemic lupus erythematosus correlates with disease activity but not with antiretroviral antibodies. Lupus 9:664–671PubMedCrossRef Bengtsson AA, Sturfelt G, Truedsson L et al (2000) Activation of type I interferon system in systemic lupus erythematosus correlates with disease activity but not with antiretroviral antibodies. Lupus 9:664–671PubMedCrossRef
57.
59.
go back to reference Lyn-Cook BD, Xie C, Oates J et al (2014) Increased expression of Toll-like receptors (TLRs) 7 and 9 and other cytokines in systemic lupus erythematosus (SLE) patients: ethnic differences and potential new targets for therapeutic drugs. Mol Immunol 61:38–43. doi:10.1016/j.molimm.2014.05.001 PubMedCrossRef Lyn-Cook BD, Xie C, Oates J et al (2014) Increased expression of Toll-like receptors (TLRs) 7 and 9 and other cytokines in systemic lupus erythematosus (SLE) patients: ethnic differences and potential new targets for therapeutic drugs. Mol Immunol 61:38–43. doi:10.​1016/​j.​molimm.​2014.​05.​001 PubMedCrossRef
60.
go back to reference Castiblanco J, Varela D-C, Castaño-Rodríguez N et al (2008) TIRAP (MAL) S180L polymorphism is a common protective factor against developing tuberculosis and systemic lupus erythematosus. Infect Genet Evol J Mol Epidemiol Evol Genet Infect Dis 8:541–544. doi:10.1016/j.meegid.2008.03.001 CrossRef Castiblanco J, Varela D-C, Castaño-Rodríguez N et al (2008) TIRAP (MAL) S180L polymorphism is a common protective factor against developing tuberculosis and systemic lupus erythematosus. Infect Genet Evol J Mol Epidemiol Evol Genet Infect Dis 8:541–544. doi:10.​1016/​j.​meegid.​2008.​03.​001 CrossRef
62.
63.
go back to reference Zhou X-J, Lv J-C, Cheng W-R et al (2010) Association of TLR9 gene polymorphisms with lupus nephritis in a Chinese Han population. Clin Exp Rheumatol 28:397–400PubMed Zhou X-J, Lv J-C, Cheng W-R et al (2010) Association of TLR9 gene polymorphisms with lupus nephritis in a Chinese Han population. Clin Exp Rheumatol 28:397–400PubMed
64.
go back to reference Laska MJ, Troldborg A, Hansen B et al (2014) Polymorphisms within Toll-like receptors are associated with systemic lupus erythematosus in a cohort of Danish females. Rheumatol Oxf Engl 53:48–55. doi:10.1093/rheumatology/ket316 CrossRef Laska MJ, Troldborg A, Hansen B et al (2014) Polymorphisms within Toll-like receptors are associated with systemic lupus erythematosus in a cohort of Danish females. Rheumatol Oxf Engl 53:48–55. doi:10.​1093/​rheumatology/​ket316 CrossRef
66.
go back to reference Zhu L, Yang X, Chen W et al (2007) Decreased expressions of the TNF-alpha signaling adapters in peripheral blood mononuclear cells (PBMCs) are correlated with disease activity in patients with systemic lupus erythematosus. Clin Rheumatol 26:1481–1489. doi:10.1007/s10067-006-0531-8 PubMedCrossRef Zhu L, Yang X, Chen W et al (2007) Decreased expressions of the TNF-alpha signaling adapters in peripheral blood mononuclear cells (PBMCs) are correlated with disease activity in patients with systemic lupus erythematosus. Clin Rheumatol 26:1481–1489. doi:10.​1007/​s10067-006-0531-8 PubMedCrossRef
67.
go back to reference Tsao J-T, Kuo C-C, Lin S-C (2008) The analysis of CIS, SOCS1, SOSC2 and SOCS3 transcript levels in peripheral blood mononuclear cells of systemic lupus erythematosus and rheumatoid arthritis patients. Clin Exp Med 8:179–185. doi:10.1007/s10238-008-0006-0 PubMedCrossRef Tsao J-T, Kuo C-C, Lin S-C (2008) The analysis of CIS, SOCS1, SOSC2 and SOCS3 transcript levels in peripheral blood mononuclear cells of systemic lupus erythematosus and rheumatoid arthritis patients. Clin Exp Med 8:179–185. doi:10.​1007/​s10238-008-0006-0 PubMedCrossRef
71.
go back to reference Gveric D, Kaltschmidt C, Cuzner ML, Newcombe J (1998) Transcription factor NF-kappaB and inhibitor I kappaBalpha are localized in macrophages in active multiple sclerosis lesions. J Neuropathol Exp Neurol 57:168–178PubMedCrossRef Gveric D, Kaltschmidt C, Cuzner ML, Newcombe J (1998) Transcription factor NF-kappaB and inhibitor I kappaBalpha are localized in macrophages in active multiple sclerosis lesions. J Neuropathol Exp Neurol 57:168–178PubMedCrossRef
72.
go back to reference Christophi GP, Panos M, Hudson CA et al (2009) Macrophages of multiple sclerosis patients display deficient SHP-1 expression and enhanced inflammatory phenotype. Lab Investig J Tech Methods Pathol 89:742–759. doi:10.1038/labinvest.2009.32 CrossRef Christophi GP, Panos M, Hudson CA et al (2009) Macrophages of multiple sclerosis patients display deficient SHP-1 expression and enhanced inflammatory phenotype. Lab Investig J Tech Methods Pathol 89:742–759. doi:10.​1038/​labinvest.​2009.​32 CrossRef
75.
go back to reference Kostjuk S, Loseva P, Chvartatskaya O et al (2012) Extracellular GC-rich DNA activates TLR9- and NF-kB-dependent signaling pathways in human adipose-derived mesenchymal stem cells (haMSCs). Expert Opin Biol Ther 12(Suppl 1):S99–111. doi:10.1517/14712598.2012.690028 PubMedCrossRef Kostjuk S, Loseva P, Chvartatskaya O et al (2012) Extracellular GC-rich DNA activates TLR9- and NF-kB-dependent signaling pathways in human adipose-derived mesenchymal stem cells (haMSCs). Expert Opin Biol Ther 12(Suppl 1):S99–111. doi:10.​1517/​14712598.​2012.​690028 PubMedCrossRef
80.
go back to reference Compton T, Kurt-Jones EA, Boehme KW et al (2003) Human cytomegalovirus activates inflammatory cytokine responses via CD14 and Toll-like receptor 2. J Virol 77:4588–4596PubMedCentralPubMedCrossRef Compton T, Kurt-Jones EA, Boehme KW et al (2003) Human cytomegalovirus activates inflammatory cytokine responses via CD14 and Toll-like receptor 2. J Virol 77:4588–4596PubMedCentralPubMedCrossRef
81.
go back to reference Dolganiuc A, Oak S, Kodys K et al (2004) Hepatitis C core and nonstructural 3 proteins trigger toll-like receptor 2-mediated pathways and inflammatory activation. Gastroenterology 127:1513–1524PubMedCrossRef Dolganiuc A, Oak S, Kodys K et al (2004) Hepatitis C core and nonstructural 3 proteins trigger toll-like receptor 2-mediated pathways and inflammatory activation. Gastroenterology 127:1513–1524PubMedCrossRef
82.
go back to reference Bieback K, Lien E, Klagge IM et al (2002) Hemagglutinin protein of wild-type measles virus activates toll-like receptor 2 signaling. J Virol 76:8729–8736PubMedCentralPubMedCrossRef Bieback K, Lien E, Klagge IM et al (2002) Hemagglutinin protein of wild-type measles virus activates toll-like receptor 2 signaling. J Virol 76:8729–8736PubMedCentralPubMedCrossRef
86.
89.
go back to reference Wesemann DR, Dong Y, O’Keefe GM et al (2002) Suppressor of cytokine signaling 1 inhibits cytokine induction of CD40 expression in macrophages. J Immunol 169:2354–2360PubMedCrossRef Wesemann DR, Dong Y, O’Keefe GM et al (2002) Suppressor of cytokine signaling 1 inhibits cytokine induction of CD40 expression in macrophages. J Immunol 169:2354–2360PubMedCrossRef
92.
go back to reference Bjørbaek C, Elmquist JK, Frantz JD et al (1998) Identification of SOCS-3 as a potential mediator of central leptin resistance. Mol Cell 1:619–625PubMedCrossRef Bjørbaek C, Elmquist JK, Frantz JD et al (1998) Identification of SOCS-3 as a potential mediator of central leptin resistance. Mol Cell 1:619–625PubMedCrossRef
94.
go back to reference Ramgolam VS, Markovic-Plese S (2010) Interferon-beta inhibits Th17 cell differentiation in patients with multiple sclerosis. Endocr Metab Immune Disord Drug Targets 10:161–167PubMedCrossRef Ramgolam VS, Markovic-Plese S (2010) Interferon-beta inhibits Th17 cell differentiation in patients with multiple sclerosis. Endocr Metab Immune Disord Drug Targets 10:161–167PubMedCrossRef
95.
go back to reference Zhang X, Jin J, Peng X et al (2008) Simvastatin inhibits IL-17 secretion by targeting multiple IL-17-regulatory cytokines and by inhibiting the expression of IL-17 transcription factor RORC in CD4+ lymphocytes. J Immunol 180:6988–6996PubMedCrossRef Zhang X, Jin J, Peng X et al (2008) Simvastatin inhibits IL-17 secretion by targeting multiple IL-17-regulatory cytokines and by inhibiting the expression of IL-17 transcription factor RORC in CD4+ lymphocytes. J Immunol 180:6988–6996PubMedCrossRef
97.
go back to reference Weber MS, Zamvil SS (2008) Statins and demyelination. Curr Top Microbiol Immunol 318:313–324PubMed Weber MS, Zamvil SS (2008) Statins and demyelination. Curr Top Microbiol Immunol 318:313–324PubMed
99.
go back to reference Gibofsky A (2012) Overview of epidemiology, pathophysiology, and diagnosis of rheumatoid arthritis. Am J Manag Care 18:S295–302PubMed Gibofsky A (2012) Overview of epidemiology, pathophysiology, and diagnosis of rheumatoid arthritis. Am J Manag Care 18:S295–302PubMed
103.
go back to reference Enevold C, Radstake TRD, Coenen MJH et al (2010) Multiplex screening of 22 single-nucleotide polymorphisms in 7 Toll-like receptors: an association study in rheumatoid arthritis. J Rheumatol 37:905–910. doi:10.3899/jrheum.090775 PubMedCrossRef Enevold C, Radstake TRD, Coenen MJH et al (2010) Multiplex screening of 22 single-nucleotide polymorphisms in 7 Toll-like receptors: an association study in rheumatoid arthritis. J Rheumatol 37:905–910. doi:10.​3899/​jrheum.​090775 PubMedCrossRef
106.
go back to reference Brentano F, Schorr O, Gay RE et al (2005) RNA released from necrotic synovial fluid cells activates rheumatoid arthritis synovial fibroblasts via Toll-like receptor 3. Arthritis Rheum 52:2656–2665. doi:10.1002/art.21273 PubMedCrossRef Brentano F, Schorr O, Gay RE et al (2005) RNA released from necrotic synovial fluid cells activates rheumatoid arthritis synovial fibroblasts via Toll-like receptor 3. Arthritis Rheum 52:2656–2665. doi:10.​1002/​art.​21273 PubMedCrossRef
107.
go back to reference Sacre SM, Lo A, Gregory B et al (2008) Inhibitors of TLR8 reduce TNF production from human rheumatoid synovial membrane cultures. J Immunol 181:8002–8009PubMedCrossRef Sacre SM, Lo A, Gregory B et al (2008) Inhibitors of TLR8 reduce TNF production from human rheumatoid synovial membrane cultures. J Immunol 181:8002–8009PubMedCrossRef
108.
go back to reference Ospelt C, Brentano F, Rengel Y et al (2008) Overexpression of toll-like receptors 3 and 4 in synovial tissue from patients with early rheumatoid arthritis: toll-like receptor expression in early and longstanding arthritis. Arthritis Rheum 58:3684–3692. doi:10.1002/art.24140 PubMedCrossRef Ospelt C, Brentano F, Rengel Y et al (2008) Overexpression of toll-like receptors 3 and 4 in synovial tissue from patients with early rheumatoid arthritis: toll-like receptor expression in early and longstanding arthritis. Arthritis Rheum 58:3684–3692. doi:10.​1002/​art.​24140 PubMedCrossRef
109.
go back to reference Roelofs MF, Wenink MH, Brentano F et al (2009) Type I interferons might form the link between Toll-like receptor (TLR) 3/7 and TLR4-mediated synovial inflammation in rheumatoid arthritis (RA). Ann Rheum Dis 68:1486–1493. doi:10.1136/ard.2007.086421 PubMedCrossRef Roelofs MF, Wenink MH, Brentano F et al (2009) Type I interferons might form the link between Toll-like receptor (TLR) 3/7 and TLR4-mediated synovial inflammation in rheumatoid arthritis (RA). Ann Rheum Dis 68:1486–1493. doi:10.​1136/​ard.​2007.​086421 PubMedCrossRef
111.
go back to reference Radstake TRDJ, Roelofs MF, Jenniskens YM et al (2004) Expression of toll-like receptors 2 and 4 in rheumatoid synovial tissue and regulation by proinflammatory cytokines interleukin-12 and interleukin-18 via interferon-gamma. Arthritis Rheum 50:3856–3865. doi:10.1002/art.20678 PubMedCrossRef Radstake TRDJ, Roelofs MF, Jenniskens YM et al (2004) Expression of toll-like receptors 2 and 4 in rheumatoid synovial tissue and regulation by proinflammatory cytokines interleukin-12 and interleukin-18 via interferon-gamma. Arthritis Rheum 50:3856–3865. doi:10.​1002/​art.​20678 PubMedCrossRef
113.
go back to reference Pierer M, Rethage J, Seibl R et al (2004) Chemokine secretion of rheumatoid arthritis synovial fibroblasts stimulated by Toll-like receptor 2 ligands. J Immunol 172:1256–1265PubMedCrossRef Pierer M, Rethage J, Seibl R et al (2004) Chemokine secretion of rheumatoid arthritis synovial fibroblasts stimulated by Toll-like receptor 2 ligands. J Immunol 172:1256–1265PubMedCrossRef
114.
go back to reference Roelofs MF, Joosten LA, Abdollahi-Roodsaz S et al (2005) The expression of toll-like receptors 3 and 7 in rheumatoid arthritis synovium is increased and costimulation of toll-like receptors 3, 4, and 7/8 results in synergistic cytokine production by dendritic cells. Arthritis Rheum 52:2313–2322. doi:10.1002/art.21278 PubMedCrossRef Roelofs MF, Joosten LA, Abdollahi-Roodsaz S et al (2005) The expression of toll-like receptors 3 and 7 in rheumatoid arthritis synovium is increased and costimulation of toll-like receptors 3, 4, and 7/8 results in synergistic cytokine production by dendritic cells. Arthritis Rheum 52:2313–2322. doi:10.​1002/​art.​21278 PubMedCrossRef
115.
go back to reference Maksymowych W, Russell AS (1987) Antimalarials in rheumatology: efficacy and safety. Semin Arthritis Rheum 16:206–221PubMedCrossRef Maksymowych W, Russell AS (1987) Antimalarials in rheumatology: efficacy and safety. Semin Arthritis Rheum 16:206–221PubMedCrossRef
116.
go back to reference Khraishi MM, Singh G (1996) The role of anti-malarials in rheumatoid arthritis—the American experience. Lupus 5(Suppl 1):S41–44PubMedCrossRef Khraishi MM, Singh G (1996) The role of anti-malarials in rheumatoid arthritis—the American experience. Lupus 5(Suppl 1):S41–44PubMedCrossRef
120.
go back to reference Raghav SK, Gupta B, Agrawal C et al (2006) Expression of TNF-alpha and related signaling molecules in the peripheral blood mononuclear cells of rheumatoid arthritis patients. Mediat Inflamm 2006:12682. doi:10.1155/MI/2006/12682 Raghav SK, Gupta B, Agrawal C et al (2006) Expression of TNF-alpha and related signaling molecules in the peripheral blood mononuclear cells of rheumatoid arthritis patients. Mediat Inflamm 2006:12682. doi:10.​1155/​MI/​2006/​12682
122.
123.
go back to reference Casale R, Buonocore M, Matucci-Cerinic M (1997) Systemic sclerosis (scleroderma): an integrated challenge in rehabilitation. Arch Phys Med Rehabil 78:767–773PubMedCrossRef Casale R, Buonocore M, Matucci-Cerinic M (1997) Systemic sclerosis (scleroderma): an integrated challenge in rehabilitation. Arch Phys Med Rehabil 78:767–773PubMedCrossRef
125.
go back to reference Broen JCA, Bossini-Castillo L, van Bon L et al (2012) A rare polymorphism in the gene for Toll-like receptor 2 is associated with systemic sclerosis phenotype and increases the production of inflammatory mediators. Arthritis Rheum 64:264–271. doi:10.1002/art.33325 PubMedCrossRef Broen JCA, Bossini-Castillo L, van Bon L et al (2012) A rare polymorphism in the gene for Toll-like receptor 2 is associated with systemic sclerosis phenotype and increases the production of inflammatory mediators. Arthritis Rheum 64:264–271. doi:10.​1002/​art.​33325 PubMedCrossRef
126.
go back to reference York MR, Nagai T, Mangini AJ et al (2007) A macrophage marker, Siglec-1, is increased on circulating monocytes in patients with systemic sclerosis and induced by type I interferons and toll-like receptor agonists. Arthritis Rheum 56:1010–1020. doi:10.1002/art.22382 PubMedCrossRef York MR, Nagai T, Mangini AJ et al (2007) A macrophage marker, Siglec-1, is increased on circulating monocytes in patients with systemic sclerosis and induced by type I interferons and toll-like receptor agonists. Arthritis Rheum 56:1010–1020. doi:10.​1002/​art.​22382 PubMedCrossRef
127.
go back to reference van Lieshout AWT, Vonk MC, Bredie SJH et al (2009) Enhanced interleukin-10 production by dendritic cells upon stimulation with Toll-like receptor 4 agonists in systemic sclerosis that is possibly implicated in CCL18 secretion. Scand J Rheumatol 38:282–290. doi:10.1080/03009740802572467 PubMedCrossRef van Lieshout AWT, Vonk MC, Bredie SJH et al (2009) Enhanced interleukin-10 production by dendritic cells upon stimulation with Toll-like receptor 4 agonists in systemic sclerosis that is possibly implicated in CCL18 secretion. Scand J Rheumatol 38:282–290. doi:10.​1080/​0300974080257246​7 PubMedCrossRef
128.
go back to reference Fineschi S, Goffin L, Rezzonico R et al (2008) Antifibroblast antibodies in systemic sclerosis induce fibroblasts to produce profibrotic chemokines, with partial exploitation of toll-like receptor 4. Arthritis Rheum 58:3913–3923. doi:10.1002/art.24049 PubMedCrossRef Fineschi S, Goffin L, Rezzonico R et al (2008) Antifibroblast antibodies in systemic sclerosis induce fibroblasts to produce profibrotic chemokines, with partial exploitation of toll-like receptor 4. Arthritis Rheum 58:3913–3923. doi:10.​1002/​art.​24049 PubMedCrossRef
131.
go back to reference Woessner JF (1991) Matrix metalloproteinases and their inhibitors in connective tissue remodeling. FASEB J Off Publ Fed Am Soc Exp Biol 5:2145–2154 Woessner JF (1991) Matrix metalloproteinases and their inhibitors in connective tissue remodeling. FASEB J Off Publ Fed Am Soc Exp Biol 5:2145–2154
132.
go back to reference Kikuchi K, Kubo M, Hoashi T, Tamaki K (2002) Decreased MMP-9 activity in the serum of patients with diffuse cutaneous systemic sclerosis. Clin Exp Dermatol 27:301–305PubMedCrossRef Kikuchi K, Kubo M, Hoashi T, Tamaki K (2002) Decreased MMP-9 activity in the serum of patients with diffuse cutaneous systemic sclerosis. Clin Exp Dermatol 27:301–305PubMedCrossRef
134.
go back to reference Kikuchi K, Kubo M, Sato S et al (1995) Serum tissue inhibitor of metalloproteinases in patients with systemic sclerosis. J Am Acad Dermatol 33:973–978PubMedCrossRef Kikuchi K, Kubo M, Sato S et al (1995) Serum tissue inhibitor of metalloproteinases in patients with systemic sclerosis. J Am Acad Dermatol 33:973–978PubMedCrossRef
135.
go back to reference Iredale JP, Benyon RC, Arthur MJ et al (1996) Tissue inhibitor of metalloproteinase-1 messenger RNA expression is enhanced relative to interstitial collagenase messenger RNA in experimental liver injury and fibrosis. Hepatolgy 24:176–184. doi:10.1002/hep.510240129, Baltim MdCrossRef Iredale JP, Benyon RC, Arthur MJ et al (1996) Tissue inhibitor of metalloproteinase-1 messenger RNA expression is enhanced relative to interstitial collagenase messenger RNA in experimental liver injury and fibrosis. Hepatolgy 24:176–184. doi:10.​1002/​hep.​510240129, Baltim MdCrossRef
137.
go back to reference Christophers E (2001) Psoriasis–epidemiology and clinical spectrum. Clin Exp Dermatol 26:314–320PubMedCrossRef Christophers E (2001) Psoriasis–epidemiology and clinical spectrum. Clin Exp Dermatol 26:314–320PubMedCrossRef
138.
go back to reference Baker BS, Ovigne J-M, Powles AV et al (2003) Normal keratinocytes express Toll-like receptors (TLRs) 1, 2 and 5: modulation of TLR expression in chronic plaque psoriasis. Br J Dermatol 148:670–679PubMedCrossRef Baker BS, Ovigne J-M, Powles AV et al (2003) Normal keratinocytes express Toll-like receptors (TLRs) 1, 2 and 5: modulation of TLR expression in chronic plaque psoriasis. Br J Dermatol 148:670–679PubMedCrossRef
142.
go back to reference Miller LS, Sørensen OE, Liu PT et al (2005) TGF-alpha regulates TLR expression and function on epidermal keratinocytes. J Immunol 174:6137–6143PubMedCrossRef Miller LS, Sørensen OE, Liu PT et al (2005) TGF-alpha regulates TLR expression and function on epidermal keratinocytes. J Immunol 174:6137–6143PubMedCrossRef
148.
go back to reference Federici M, Giustizieri ML, Scarponi C et al (2002) Impaired IFN-gamma-dependent inflammatory responses in human keratinocytes overexpressing the suppressor of cytokine signaling 1. J Immunol 169:434–442PubMedCrossRef Federici M, Giustizieri ML, Scarponi C et al (2002) Impaired IFN-gamma-dependent inflammatory responses in human keratinocytes overexpressing the suppressor of cytokine signaling 1. J Immunol 169:434–442PubMedCrossRef
150.
go back to reference Begon E, Michel L, Flageul B et al (2007) Expression, subcellular localization and cytokinic modulation of Toll-like receptors (TLRs) in normal human keratinocytes: TLR2 up-regulation in psoriatic skin. Eur J Dermatol EJD 17:497–506. doi:10.1684/ejd.2007.0264 PubMed Begon E, Michel L, Flageul B et al (2007) Expression, subcellular localization and cytokinic modulation of Toll-like receptors (TLRs) in normal human keratinocytes: TLR2 up-regulation in psoriatic skin. Eur J Dermatol EJD 17:497–506. doi:10.​1684/​ejd.​2007.​0264 PubMed
153.
go back to reference Litjens NHR, Rademaker M, Ravensbergen B et al (2004) Monomethylfumarate affects polarization of monocyte-derived dendritic cells resulting in down-regulated Th1 lymphocyte responses. Eur J Immunol 34:565–575. doi:10.1002/eji.200324174 PubMedCrossRef Litjens NHR, Rademaker M, Ravensbergen B et al (2004) Monomethylfumarate affects polarization of monocyte-derived dendritic cells resulting in down-regulated Th1 lymphocyte responses. Eur J Immunol 34:565–575. doi:10.​1002/​eji.​200324174 PubMedCrossRef
Metadata
Title
Toll-Like Receptor Pathways in Autoimmune Diseases
Authors
Ji-Qing Chen
Peter Szodoray
Margit Zeher
Publication date
01-02-2016
Publisher
Springer US
Published in
Clinical Reviews in Allergy & Immunology / Issue 1/2016
Print ISSN: 1080-0549
Electronic ISSN: 1559-0267
DOI
https://doi.org/10.1007/s12016-015-8473-z

Other articles of this Issue 1/2016

Clinical Reviews in Allergy & Immunology 1/2016 Go to the issue
Obesity Clinical Trial Summary

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.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.