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Autoimmunity Highlights
Published in: Autoimmunity Highlights 1/2018

Open Access 01-12-2018 | Review Article

Regulatory B and T lymphocytes in multiple sclerosis: friends or foes?

Authors: Georgios K. Vasileiadis, Efthymios Dardiotis, Athanasios Mavropoulos, Zisis Tsouris, Vana Tsimourtou, Dimitrios P. Bogdanos, Lazaros I. Sakkas, Georgios M. Hadjigeorgiou

Published in: Autoimmunity Highlights | Issue 1/2018

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Abstract

Current clinical experience with immunomodulatory agents and monoclonal antibodies in principle has established the benefit of depleting lymphocytic populations in relapsing–remitting multiple sclerosis (RRMS). B and T cells may exert multiple pro-inflammatory actions, but also possess regulatory functions making their role in RRMS pathogenesis much more complex. There is no clear correlation of Tregs and Bregs with clinical features of the disease. Herein, we discuss the emerging data on regulatory T and B cell subset distributions in MS and their roles in the pathophysiology of MS and its murine model, experimental autoimmune encephalomyelitis (EAE). In addition, we summarize the immunomodulatory properties of certain MS therapeutic agents through their effect on such regulatory cell subsets and their relevance to clinical outcomes.
Literature
1.
Compston A, Coles A (2008) Multiple sclerosis. Lancet 372(9648):1502–1517PubMed
2.
Giovannoni G, Miller DH (1999) Multiple sclerosis and its treatment. J R Coll Physicians Lond 33(4):315–322PubMed
3.
Francis DA (2001) Glatiramer acetate (Copaxone). Int J Clin Pract 55(6):394–398PubMed
4.
Signori A, Gallo F, Bovis F, Di Tullio N, Maietta I, Sormani MP (2016) Long-term impact of interferon or Glatiramer acetate in multiple sclerosis: a systematic review and meta-analysis. Mult Scler Relat Disord 6:57–63PubMed
5.
Castillo-Trivino T, Braithwaite D, Bacchetti P, Waubant E (2013) Rituximab in relapsing and progressive forms of multiple sclerosis: a systematic review. PLoS One 8(7):e66308PubMedPubMedCentral
6.
Havrdova E, Horakova D, Kovarova I (2015) Alemtuzumab in the treatment of multiple sclerosis: key clinical trial results and considerations for use. Ther Adv Neurol Disord 8(1):31–45PubMedPubMedCentral
7.
Coles AJ (2013) Alemtuzumab therapy for multiple sclerosis. Neurotherapeutics 10(1):29–33PubMed
8.
Blumenfeld S, Staun-Ram E, Miller A (2016) Fingolimod therapy modulates circulating B cell composition, increases B regulatory subsets and production of IL-10 and TGFbeta in patients with multiple sclerosis. J Autoimmun 70:40–51PubMed
9.
Gross CC, Schulte-Mecklenbeck A, Klinsing S, Posevitz-Fejfar A, Wiendl H, Klotz L (2016) Dimethyl fumarate treatment alters circulating T helper cell subsets in multiple sclerosis. Neurol Neuroimmunol Neuroinflammation 3(1):e183
10.
Oh J, O’Connor PW (2014) Teriflunomide in the treatment of multiple sclerosis: current evidence and future prospects. Ther Adv Neurol Disord 7(5):239–252PubMedPubMedCentral
11.
12.
Midaglia L, Mora L, Mulero P, Sastre-Garriga J, Montalban X (2018) Rituximab: its efficacy, effectiveness and safety in the treatment of multiple sclerosis. Rev Neurol 66(1):25–32PubMed
13.
Sokratous M, Dardiotis E, Tsouris Z, Bellou E, Michalopoulou A, Siokas V et al (2016) Deciphering the role of DNA methylation in multiple sclerosis: emerging issues. Auto Immun Highlights 7(1):12PubMedPubMedCentral
14.
Baecher-Allan C, Kaskow BJ, Weiner HL (2018) Multiple sclerosis: mechanisms and immunotherapy. Neuron 97(4):742–768PubMed
15.
Naegele M, Martin R (2014) The good and the bad of neuroinflammation in multiple sclerosis. Handb Clin Neurol 122:59–87PubMed
16.
Hedegaard CJ, Krakauer M, Bendtzen K, Lund H, Sellebjerg F, Nielsen CH (2008) T helper cell type 1 (Th1), Th2 and Th17 responses to myelin basic protein and disease activity in multiple sclerosis. Immunology 125(2):161–169PubMedPubMedCentral
17.
Drulovic J, Savic E, Pekmezovic T, Mesaros S, Stojsavljevic N, Dujmovic-Basuroski I et al (2009) Expression of Th1 and Th17 cytokines and transcription factors in multiple sclerosis patients: does baseline T-bet mRNA predict the response to interferon-beta treatment? J Neuroimmunol 215(1–2):90–95PubMed
18.
Peelen E, Damoiseaux J, Smolders J, Knippenberg S, Menheere P, Tervaert JW et al (2011) Th17 expansion in MS patients is counterbalanced by an expanded CD39+regulatory T cell population during remission but not during relapse. J Neuroimmunol 240–241:97–103PubMed
19.
20.
von Budingen HC, Kuo TC, Sirota M, van Belle CJ, Apeltsin L, Glanville J et al (2012) B cell exchange across the blood-brain barrier in multiple sclerosis. J Clin Investig 122(12):4533–4543
21.
Staun-Ram E, Miller A (2017) Effector and regulatory B cells in multiple sclerosis. Clin Immunol 184:11–25PubMed
22.
Sospedra M (2018) B cells in multiple sclerosis. Curr Opin Neurol 31(3):256–262PubMed
23.
Batista FD, Harwood NE (2009) The who, how and where of antigen presentation to B cells. Nat Rev Immunol 9(1):15–27PubMed
24.
Meinl E, Krumbholz M, Hohlfeld R (2006) B lineage cells in the inflammatory central nervous system environment: migration, maintenance, local antibody production, and therapeutic modulation. Ann Neurol 59(6):880–892PubMed
25.
Barr TA, Shen P, Brown S, Lampropoulou V, Roch T, Lawrie S et al (2012) B cell depletion therapy ameliorates autoimmune disease through ablation of IL-6-producing B cells. J Exp Med 209(5):1001–1010PubMedPubMedCentral
26.
Mielle J, Audo R, Hahne M, Macia L, Combe B, Morel J et al (2018) IL-10 producing B cells ability to induce regulatory T cells is maintained in rheumatoid arthritis. Front Immunol 9:961PubMedPubMedCentral
27.
Romme Christensen J, Bornsen L, Hesse D, Krakauer M, Sorensen PS, Sondergaard HB et al (2012) Cellular sources of dysregulated cytokines in relapsing-remitting multiple sclerosis. J Neuroinflammation 9:215PubMedPubMedCentral
28.
Claes N, Fraussen J, Stinissen P, Hupperts R, Somers V (2015) B cells are multifunctional players in multiple sclerosis pathogenesis: insights from therapeutic interventions. Front Immunol 6:642PubMedPubMedCentral
29.
30.
Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M (1995) Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol 155(3):1151–1164PubMed
31.
Grant CR, Liberal R, Mieli-Vergani G, Vergani D, Longhi MS (2015) Regulatory T-cells in autoimmune diseases: challenges, controversies and–yet–unanswered questions. Autoimmun Rev 14(2):105–116PubMed
32.
Su H, Longhi MS, Wang P, Vergani D, Ma Y (2012) Human CD4+CD25(high)CD127 (low/neg) regulatory T cells. Methods Mol Biol 806:287–299PubMed
33.
Yates J, Rovis F, Mitchell P, Afzali B, Tsang J, Garin M et al (2007) The maintenance of human CD4+CD25+ regulatory T cell function: IL-2, IL-4, IL-7 and IL-15 preserve optimal suppressive potency in vitro. Int Immunol 19(6):785–799PubMed
34.
Lee J, Park N, Park JY, Kaplan BLF, Pruett SB, Park JW et al (2018) Induction of immunosuppressive CD8(+)CD25(+)FOXP3(+) regulatory T cells by suboptimal stimulation with staphylococcal enterotoxin C1. J Immunol 200(2):669–680PubMed
35.
Saverino D, Simone R, Bagnasco M, Pesce G (2010) The soluble CTLA-4 receptor and its role in autoimmune diseases: an update. Auto Immun Highlights 1(2):73–81PubMedPubMedCentral
36.
Takahashi T, Tagami T, Yamazaki S, Uede T, Shimizu J, Sakaguchi N et al (2000) Immunologic self-tolerance maintained by CD25(+)CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4. J Exp Med 192(2):303–310PubMedPubMedCentral
37.
Qiao YC, Pan YH, Ling W, Tian F, Chen YL, Zhang XX et al (2017) The Yin and Yang of regulatory T cell and therapy progress in autoimmune disease. Autoimmun Rev 16(10):1058–1070PubMed
38.
Henderson JG, Opejin A, Jones A, Gross C, Hawiger D (2015) CD5 instructs extrathymic regulatory T cell development in response to self and tolerizing antigens. Immunity 42(3):471–483PubMed
39.
Ono M, Tanaka RJ (2016) Controversies concerning thymus-derived regulatory T cells: fundamental issues and a new perspective. Immunol Cell Biol 94(1):3–10PubMed
40.
Xing C, Ma N, Xiao H, Wang X, Zheng M, Han G et al (2015) Critical role for thymic CD19+CD5+CD1dhiIL-10+ regulatory B cells in immune homeostasis. J Leukoc Biol 97(3):547–556PubMed
41.
Zheng M, Xing C, Xiao H, Ma N, Wang X, Han G et al (2014) Interaction of CD5 and CD72 is involved in regulatory T and B cell homeostasis. Immunol Invest 43(7):705–716PubMed
42.
Fontenot JD, Gavin MA, Rudensky AY (2003) Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol 4(4):330–336PubMed
43.
Devaud C, Darcy PK, Kershaw MH (2014) Foxp3 expression in T regulatory cells and other cell lineages. Cancer Immunol Immunother CII 63(9):869–876PubMed
44.
Borsellino G, Kleinewietfeld M, Di Mitri D, Sternjak A, Diamantini A, Giometto R et al (2007) Expression of ectonucleotidase CD39 by Foxp3+Treg cells: hydrolysis of extracellular ATP and immune suppression. Blood 110(4):1225–1232PubMed
45.
Okamura T, Fujio K, Shibuya M, Sumitomo S, Shoda H, Sakaguchi S et al (2009) CD4+CD25-LAG3+ regulatory T cells controlled by the transcription factor Egr-2. Proc Natl Acad Sci U S A 106(33):13974–13979PubMedPubMedCentral
46.
Bushell A, Wood K (2007) GITR ligation blocks allograft protection by induced CD25+CD4+ regulatory T cells without enhancing effector T-cell function. Am J Transpl 7(4):759–768
47.
Anvari S, Grimbergen A, Davis CM, Makedonas G (2017) Protein transport inhibitors downregulate the expression of LAG-3 on regulatory T cells. J Immunol Methods 447:47–51PubMed
48.
Bilate AM, Lafaille JJ (2012) Induced CD4+Foxp3+ regulatory T cells in immune tolerance. Annu Rev Immunol 30:733–758PubMed
49.
Miyara M, Yoshioka Y, Kitoh A, Shima T, Wing K, Niwa A et al (2009) Functional delineation and differentiation dynamics of human CD4+T cells expressing the FoxP3 transcription factor. Immunity 30(6):899–911PubMed
50.
Okamura T, Yamamoto K, Fujio K (2018) Early growth response gene 2-expressing CD4(+)LAG3(+) regulatory T cells: the therapeutic potential for treating autoimmune diseases. Front Immunol 9:340PubMedPubMedCentral
51.
52.
Kanamori M, Nakatsukasa H, Okada M, Lu Q, Yoshimura A (2016) Induced regulatory T cells: their development, stability, and applications. Trends Immunol 37(11):803–811PubMed
53.
54.
Mayo L, Cunha AP, Madi A, Beynon V, Yang Z, Alvarez JI et al (2016) IL-10-dependent Tr1 cells attenuate astrocyte activation and ameliorate chronic central nervous system inflammation. Brain 139(Pt 7):1939–1957PubMedPubMedCentral
55.
Fujio K, Yamamoto K, Okamura T (2017) Overview of LAG-3-expressing, IL-10-producing regulatory T cells. Curr Top Microbiol Immunol 410:29–45PubMed
56.
Roncarolo MG, Gregori S, Bacchetta R, Battaglia M (2014) Tr1 cells and the counter-regulation of immunity: natural mechanisms and therapeutic applications. Curr Top Microbiol Immunol 380:39–68PubMed
57.
Zhang H, Kong H, Zeng X, Guo L, Sun X, He S (2014) Subsets of regulatory T cells and their roles in allergy. J Transl Med 12:125PubMedPubMedCentral
58.
Park JH, Eberl G (2018) Type 3 regulatory T cells at the interface of symbiosis. J Microbiol 56(3):163–171PubMed
59.
Yang BH, Hagemann S, Mamareli P, Lauer U, Hoffmann U, Beckstette M et al (2016) Foxp3(+) T cells expressing RORgammat represent a stable regulatory T-cell effector lineage with enhanced suppressive capacity during intestinal inflammation. Mucosal Immunol 9(2):444–457PubMed
60.
61.
Collison LW, Workman CJ, Kuo TT, Boyd K, Wang Y, Vignali KM et al (2007) The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature 450(7169):566–569PubMed
62.
Choi J, Leung PS, Bowlus C, Gershwin ME (2015) IL-35 and autoimmunity: a comprehensive perspective. Clin Rev Allergy Immunol 49(3):327–332PubMed
63.
Sakkas LI, Mavropoulos A, Perricone C, Bogdanos DP (2018) IL-35: a new immunomodulator in autoimmune rheumatic diseases. Immunol Res 66(3):305–312PubMed
64.
Wei X, Zhang J, Gu Q, Huang M, Zhang W, Guo J et al (2017) Reciprocal expression of IL-35 and IL-10 defines two distinct effector treg subsets that are required for maintenance of immune tolerance. Cell Rep 21(7):1853–1869PubMed
65.
Choi JK, Dambuza IM, He C, Yu CR, Uche AN, Mattapallil MJ et al (2017) IL-12p35 inhibits neuroinflammation and ameliorates autoimmune encephalomyelitis. Front Immunol 8:1258PubMedPubMedCentral
66.
Procaccini C, De Rosa V, Pucino V, Formisano L, Matarese G (2015) Animal models of multiple sclerosis. Eur J Pharmacol 759:182–191PubMedPubMedCentral
67.
Rangachari M, Kuchroo VK (2013) Using EAE to better understand principles of immune function and autoimmune pathology. J Autoimmun 45:31–39PubMedPubMedCentral
68.
Ben-Nun A, Kaushansky N, Kawakami N, Krishnamoorthy G, Berer K, Liblau R et al (2014) From classic to spontaneous and humanized models of multiple sclerosis: impact on understanding pathogenesis and drug development. J Autoimmun 54:33–50PubMed
69.
Reddy J, Illes Z, Zhang X, Encinas J, Pyrdol J, Nicholson L et al (2004) Myelin proteolipid protein-specific CD4+CD25+ regulatory cells mediate genetic resistance to experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A 101(43):15434–15439PubMedPubMedCentral
70.
Kohm AP, Carpentier PA, Anger HA, Miller SD (2002) Cutting edge: CD4+CD25+ regulatory T cells suppress antigen-specific autoreactive immune responses and central nervous system inflammation during active experimental autoimmune encephalomyelitis. J Immunol 169(9):4712–4716PubMed
71.
Korn T, Anderson AC, Bettelli E, Oukka M (2007) The dynamics of effector T cells and Foxp3+ regulatory T cells in the promotion and regulation of autoimmune encephalomyelitis. J Neuroimmunol 191(1–2):51–60PubMedPubMedCentral
72.
Montero E, Nussbaum G, Kaye JF, Perez R, Lage A, Ben-Nun A et al (2004) Regulation of experimental autoimmune encephalomyelitis by CD4+, CD25+ and CD8+T cells: analysis using depleting antibodies. J Autoimmun 23(1):1–7PubMed
73.
Zhang R, Tian A, Wang J, Shen X, Qi G, Tang Y (2015) miR26a modulates Th17/T reg balance in the EAE model of multiple sclerosis by targeting IL6. Neuromolecular Med 17(1):24–34PubMed
74.
Danikowski KM, Jayaraman S, Prabhakar BS (2017) Regulatory T cells in multiple sclerosis and myasthenia gravis. J Neuroinflammation 14(1):117PubMedPubMedCentral
75.
Yan Y, Zhang GX, Gran B, Fallarino F, Yu S, Li H et al (2010) IDO upregulates regulatory T cells via tryptophan catabolite and suppresses encephalitogenic T cell responses in experimental autoimmune encephalomyelitis. J Immunol 185(10):5953–5961PubMed
76.
Abdolahi M, Yavari P, Honarvar NM, Bitarafan S, Mahmoudi M, Saboor-Yaraghi AA (2015) Molecular mechanisms of the action of vitamin A in Th17/Treg axis in multiple sclerosis. J Mol Neurosci 57(4):605–613PubMed
77.
Kim YC, Zhang AH, Yoon J, Culp WE, Lees JR, Wucherpfennig KW et al (2018) Engineered MBP-specific human Tregs ameliorate MOG-induced EAE through IL-2-triggered inhibition of effector T cells. J Autoimmun 92:77–86PubMedPubMedCentral
78.
LaMothe RA, Kolte PN, Vo T, Ferrari JD, Gelsinger TC, Wong J et al (2018) Tolerogenic Nanoparticles induce antigen-specific regulatory T cells and provide therapeutic efficacy and transferrable tolerance against experimental autoimmune encephalomyelitis. Front Immunol 9:281PubMedPubMedCentral
79.
Feger U, Luther C, Poeschel S, Melms A, Tolosa E, Wiendl H (2007) Increased frequency of CD4+CD25+ regulatory T cells in the cerebrospinal fluid but not in the blood of multiple sclerosis patients. Clin Exp Immunol 147(3):412–418PubMedPubMedCentral
80.
Anderton SM (2010) Treg and T-effector cells in autoimmune CNS inflammation: a delicate balance, easily disturbed. Eur J Immunol 40(12):3321–3324PubMed
81.
Venken K, Hellings N, Liblau R, Stinissen P (2010) Disturbed regulatory T cell homeostasis in multiple sclerosis. Trends Mol Med 16(2):58–68PubMed
82.
Viglietta V, Baecher-Allan C, Weiner HL, Hafler DA (2004) Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis. J Exp Med 199(7):971–979PubMedPubMedCentral
83.
84.
Ochoa-Reparaz J, Kasper LH (2017) The influence of gut-derived CD39 regulatory T cells in CNS demyelinating disease. Transl Res 179:126–138PubMed
85.
Venken K, Hellings N, Thewissen M, Somers V, Hensen K, Rummens JL et al (2008) Compromised CD4+CD25(high) regulatory T-cell function in patients with relapsing-remitting multiple sclerosis is correlated with a reduced frequency of FOXP3-positive cells and reduced FOXP3 expression at the single-cell level. Immunology 123(1):79–89PubMedPubMedCentral
86.
Frisullo G, Nociti V, Iorio R, Patanella AK, Caggiula M, Marti A et al (2009) Regulatory T cells fail to suppress CD4T+-bet+T cells in relapsing multiple sclerosis patients. Immunology 127(3):418–428PubMedPubMedCentral
87.
Haas J, Fritzsching B, Trubswetter P, Korporal M, Milkova L, Fritz B et al (2007) Prevalence of newly generated naive regulatory T cells (Treg) is critical for Treg suppressive function and determines Treg dysfunction in multiple sclerosis. J Immunol 179(2):1322–1330PubMed
88.
Nicoletti F, Patti F, Cocuzza C, Zaccone P, Nicoletti A, Di Marco R et al (1996) Elevated serum levels of interleukin-12 in chronic progressive multiple sclerosis. J Neuroimmunol 70(1):87–90PubMed
89.
Dominguez-Villar M, Baecher-Allan CM, Hafler DA (2011) Identification of T helper type 1-like, Foxp3+ regulatory T cells in human autoimmune disease. Nat Med 17(6):673–675PubMedPubMedCentral
90.
Kitz A, Dominguez-Villar M (2017) Molecular mechanisms underlying Th1-like Treg generation and function. Cell Mol Life Sci 74(22):4059–4075PubMedPubMedCentral
91.
McClymont SA, Putnam AL, Lee MR, Esensten JH, Liu W, Hulme MA et al (2011) Plasticity of human regulatory T cells in healthy subjects and patients with type 1 diabetes. J Immunol 186(7):3918–3926PubMed
92.
De Matteis S, Molinari C, Abbati G, Rossi T, Napolitano R, Ghetti M et al (2018) Immunosuppressive Treg cells acquire the phenotype of effector-T cells in chronic lymphocytic leukemia patients. J Transl Med 16(1):172PubMedPubMedCentral
93.
Beriou G, Costantino CM, Ashley CW, Yang L, Kuchroo VK, Baecher-Allan C et al (2009) IL-17-producing human peripheral regulatory T cells retain suppressive function. Blood 113(18):4240–4249PubMedPubMedCentral
94.
Kleinewietfeld M, Hafler DA (2013) The plasticity of human Treg and Th17 cells and its role in autoimmunity. Semin Immunol 25(4):305–312PubMedPubMedCentral
95.
Kemper C, Chan AC, Green JM, Brett KA, Murphy KM, Atkinson JP (2003) Activation of human CD4+ cells with CD3 and CD46 induces a T-regulatory cell 1 phenotype. Nature 421(6921):388–392PubMed
96.
Mauri C, Menon M (2017) Human regulatory B cells in health and disease: therapeutic potential. J Clin Investig 127(3):772–779PubMedPubMedCentral
97.
Kalampokis I, Yoshizaki A, Tedder TF (2013) IL-10-producing regulatory B cells (B10 cells) in autoimmune disease. Arthritis Res Ther 15(Suppl 1):S1PubMedPubMedCentral
98.
Bjarnadottir K, Benkhoucha M, Merkler D, Weber MS, Payne NL, Bernard CC et al (2016) B cell-derived transforming growth factor-beta1 expression limits the induction phase of autoimmune neuroinflammation. Sci Rep 6:34594PubMedPubMedCentral
99.
Sarvaria A, Madrigal JA, Saudemont A (2017) B cell regulation in cancer and anti-tumor immunity. Cell Mol Immunol 14(8):662–674PubMedPubMedCentral
100.
Fillatreau S (2016) Regulatory roles of B cells in infectious diseases. Clin Exp Rheumatol 34(4 Suppl 98):1–5PubMed
101.
Wortel CM, Heidt S (2017) Regulatory B cells: phenotype, function and role in transplantation. Transpl Immunol 41:1–9PubMed
102.
Gallego-Valle J, Perez-Fernandez VA, Correa-Rocha R, Pion M (2018) Generation of human breg-like phenotype with regulatory function in vitro with bacteria-derived oligodeoxynucleotides. Int J Mol Sci 19(6):1737PubMedCentral
103.
Vadasz Z, Toubi E (2017) FoxP3 expression in macrophages, cancer, and B cells-is it real? Clin Rev Allergy Immunol 52(3):364–372PubMed
104.
Flores-Borja F, Bosma A, Ng D, Reddy V, Ehrenstein, Isenberg DA et al (2013) CD19+CD24hiCD38hi B cells maintain regulatory T cells while limiting TH1 and TH17 differentiation. Sci Transl Med 5(173):173ra23PubMed
105.
Iwata Y, Matsushita T, Horikawa M, Dilillo DJ, Yanaba K, Venturi GM et al (2011) Characterization of a rare IL-10-competent B-cell subset in humans that parallels mouse regulatory B10 cells. Blood 117(2):530–541PubMedPubMedCentral
106.
Rosser EC, Mauri C (2015) Regulatory B cells: origin, phenotype, and function. Immunity 42(4):607–612PubMed
107.
Dominguez-Pantoja M, Lopez-Herrera G, Romero-Ramirez H, Santos-Argumedo L, Chavez-Rueda AK, Hernandez-Cueto A et al (2018) CD38 protein deficiency induces autoimmune characteristics and its activation enhances IL-10 production by regulatory B cells. Scand J Immunol 87(6):e12664PubMed
108.
Qin J, Zhou J, Fan C, Zhao N, Liu Y, Wang S et al (2017) Increased circulating Th17 but decreased CD4(+)Foxp3(+) Treg and CD19(+)CD1d(hi)CD5(+) Breg subsets in new-onset graves’ disease. Biomed Res Int 2017:8431838PubMedPubMedCentral
109.
Han J, Sun L, Wang Z, Fan X, Wang L, Song YY et al (2017) Circulating regulatory B cell subsets in patients with neuromyelitis optica spectrum disorders. Neurol Sci 38(7):1205–1212PubMed
110.
Zhang Y, Li J, Zhou N, Zhang Y, Wu M, Xu J et al (2017) The unknown aspect of BAFF: inducing IL-35 production by a CD5(+)CD1d(hi)FcgammaRIIb(hi) regulatory B-Cell subset in Lupus. J Invest Dermatol 137(12):2532–2543PubMed
111.
Natarajan P, Singh A, McNamara JT, Secor ER Jr, Guernsey LA, Thrall RS et al (2012) Regulatory B cells from hilar lymph nodes of tolerant mice in a murine model of allergic airway disease are CD5+, express TGF-beta, and co-localize with CD4+Foxp3+T cells. Mucosal Immunol 5(6):691–701PubMedPubMedCentral
112.
Kessel A, Haj T, Peri R, Snir A, Melamed D, Sabo E et al (2012) Human CD19(+)CD25(high) B regulatory cells suppress proliferation of CD4(+) T cells and enhance Foxp3 and CTLA-4 expression in T-regulatory cells. Autoimmun Rev 11(9):670–677PubMed
113.
Lino AC, Dang VD, Lampropoulou V, Welle A, Joedicke J, Pohar J et al (2018) LAG-3 inhibitory receptor expression identifies immunosuppressive natural regulatory plasma cells. Immunity 49(1):120–133PubMedPubMedCentral
114.
van de Veen W (2017) The role of regulatory B cells in allergen immunotherapy. Curr Opin Allergy Clin Immunol 17(6):447–452PubMed
115.
van de Veen W, Stanic B, Wirz OF, Jansen K, Globinska A, Akdis M (2016) Role of regulatory B cells in immune tolerance to allergens and beyond. J Allergy Clin Immunol 138(3):654–665PubMed
116.
Matsumoto M, Baba A, Yokota T, Nishikawa H, Ohkawa Y, Kayama H et al (2014) Interleukin-10-producing plasmablasts exert regulatory function in autoimmune inflammation. Immunity 41(6):1040–1051PubMed
117.
Carter NA, Vasconcellos R, Rosser EC, Tulone C, Munoz-Suano A, Kamanaka M et al (2011) Mice lacking endogenous IL-10-producing regulatory B cells develop exacerbated disease and present with an increased frequency of Th1/Th17 but a decrease in regulatory T cells. J Immunol 186(10):5569–5579PubMed
118.
Liu Y, Cheng LS, Wu SD, Wang SQ, Li L, She WM et al (2016) IL-10-producing regulatory B-cells suppressed effector T-cells but enhanced regulatory T-cells in chronic HBV infection. Clin Sci (Lond) 130(11):907–919
119.
Aravena O, Ferrier A, Menon M, Mauri C, Aguillon JC, Soto L et al (2017) TIM-1 defines a human regulatory B cell population that is altered in frequency and function in systemic sclerosis patients. Arthritis Res Ther 19(1):8PubMedPubMedCentral
120.
Tarique M, Naz H, Kurra SV, Saini C, Naqvi RA, Rai R et al (2018) Interleukin-10 producing regulatory B cells transformed CD4(+)CD25(-) into tregs and enhanced regulatory T cells function in human leprosy. Front Immunol 9:1636PubMedPubMedCentral
121.
Moore C, Sauma D, Reyes PA, Morales J, Rosemblatt M, Bono MR et al (2010) Dendritic cells and B cells cooperate in the generation of CD4(+)CD25(+)FOXP3(+) allogeneic T cells. Transpl Proc 42(1):371–375
122.
Tian J, Zekzer D, Hanssen L, Lu Y, Olcott A, Kaufman DL (2001) Lipopolysaccharide-activated B cells down-regulate Th1 immunity and prevent autoimmune diabetes in nonobese diabetic mice. J Immunol 167(2):1081–1089PubMed
123.
Parekh VV, Prasad DV, Banerjee PP, Joshi BN, Kumar A, Mishra GC (2003) B cells activated by lipopolysaccharide, but not by anti-Ig and anti-CD40 antibody, induce anergy in CD8+T cells: role of TGF-beta 1. J Immunol 170(12):5897–5911PubMed
124.
Fillatreau S, Sweenie CH, McGeachy MJ, Gray D, Anderton SM (2002) B cells regulate autoimmunity by provision of IL-10. Nat Immunol 3(10):944–950PubMed
125.
Matsushita T, Yanaba K, Bouaziz JD, Fujimoto M, Tedder TF (2008) Regulatory B cells inhibit EAE initiation in mice while other B cells promote disease progression. J Clin Investig 118(10):3420–3430PubMedPubMedCentral
126.
Tedder TF (2015) B10 cells: a functionally defined regulatory B cell subset. J Immunol 194(4):1395–1401PubMed
127.
Egwuagu CE, Yu CR (2015) Interleukin 35-producing B Cells (i35-Breg): a new mediator of regulatory B-cell functions in CNS autoimmune diseases. Crit Rev Immunol 35(1):49–57PubMedPubMedCentral
128.
Khan AR, Hams E, Floudas A, Sparwasser T, Weaver CT, Fallon PG (2015) PD-L1hi B cells are critical regulators of humoral immunity. Nat Commun 6:5997PubMed
129.
Ray A, Wang L, Dittel BN (2015) IL-10-independent regulatory B-cell subsets and mechanisms of action. Int Immunol 27(10):531–536PubMed
130.
Murphy KM, Nelson CA, Sedy JR (2006) Balancing co-stimulation and inhibition with BTLA and HVEM. Nat Rev Immunol 6(9):671–681PubMed
131.
M’Hidi H, Thibult ML, Chetaille B, Rey F, Bouadallah R, Nicollas R et al (2009) High expression of the inhibitory receptor BTLA in T-follicular helper cells and in B-cell small lymphocytic lymphoma/chronic lymphocytic leukemia. Am J Clin Pathol 132(4):589–596PubMed
132.
Pennati A, Ng S, Wu Y, Murphy JR, Deng J, Rangaraju S et al (2016) Regulatory B cells induce formation of IL-10-expressing T cells in mice with autoimmune neuroinflammation. J Neurosci 36(50):12598–12610PubMedPubMedCentral
133.
Huarte E, Jun S, Rynda-Apple A, Golden S, Jackiw L, Hoffman C et al (2016) Regulatory T cell dysfunction Acquiesces to BTLA+regulatory B cells subsequent to oral intervention in experimental autoimmune encephalomyelitis. J Immunol 196(12):5036–5046PubMed
134.
Ray A, Mann MK, Basu S, Dittel BN (2011) A case for regulatory B cells in controlling the severity of autoimmune-mediated inflammation in experimental autoimmune encephalomyelitis and multiple sclerosis. J Neuroimmunol 230(1–2):1–9PubMed
135.
Han J, Sun L, Fan X, Wang Z, Cheng Y, Zhu J et al (2016) Role of regulatory b cells in neuroimmunologic disorders. J Neurosci Res 94(8):693–701PubMedPubMedCentral
136.
Mavropoulos A, Simopoulou T, Varna A, Liaskos C, Katsiari CG, Bogdanos DP et al (2016) Breg cells are numerically decreased and functionally impaired in patients with systemic sclerosis. Arthritis Rheumatol 68(2):494–504PubMed
137.
Blair PA, Norena LY, Flores-Borja F, Rawlings DJ, Isenberg DA, Ehrenstein MR et al (2010) CD19(+)CD24(hi)CD38(hi) B cells exhibit regulatory capacity in healthy individuals but are functionally impaired in systemic lupus erythematosus patients. Immunity 32(1):129–140PubMed
138.
Li W, Tian X, Lu X, Peng Q, Shu X, Yang H et al (2016) Significant decrease in peripheral regulatory B cells is an immunopathogenic feature of dermatomyositis. Sci Rep 6:27479PubMedPubMedCentral
139.
Mavropoulos A, Varna A, Zafiriou E, Liaskos C, Alexiou I, Roussaki-Schulze A et al (2017) IL-10 producing Bregs are impaired in psoriatic arthritis and psoriasis and inversely correlate with IL-17- and IFNgamma-producing T cells. Clin Immunol 184:33–41PubMed
140.
Daien CI, Gailhac S, Mura T, Audo R, Combe B, Hahne M et al (2014) Regulatory B10 cells are decreased in patients with rheumatoid arthritis and are inversely correlated with disease activity. Arthritis Rheumatol 66(8):2037–2046PubMed
141.
Knippenberg S, Peelen E, Smolders J, Thewissen M, Menheere P, Cohen Tervaert JW et al (2011) Reduction in IL-10 producing B cells (Breg) in multiple sclerosis is accompanied by a reduced naive/memory Breg ratio during a relapse but not in remission. J Neuroimmunol 239(1–2):80–86PubMed
142.
Piancone F, Saresella M, Marventano I, La Rosa F, Zoppis M, Agostini S et al (2016) B lymphocytes in multiple sclerosis: bregs and BTLA/CD272 expressing-CD19+lymphocytes modulate disease severity. Sci Rep 6:29699PubMedPubMedCentral
143.
Michel L, Chesneau M, Manceau P, Genty A, Garcia A, Salou M et al (2014) Unaltered regulatory B-cell frequency and function in patients with multiple sclerosis. Clin Immunol 155(2):198–208PubMed
144.
145.
de Andres C, Tejera-Alhambra M, Alonso B, Valor L, Teijeiro R, Ramos-Medina R et al (2014) New regulatory CD19(+)CD25(+) B-cell subset in clinically isolated syndrome and multiple sclerosis relapse. changes after glucocorticoids. J Neuroimmunol 270(1–2):37–44PubMed
146.
Kinnunen T, Chamberlain N, Morbach H, Cantaert T, Lynch M, Preston-Hurlburt P et al (2013) Specific peripheral B cell tolerance defects in patients with multiple sclerosis. J Clin Investig 123(6):2737–2741PubMedPubMedCentral
147.
Hirotani M, Niino M, Fukazawa T, Kikuchi S, Yabe I, Hamada S et al (2010) Decreased IL-10 production mediated by Toll-like receptor 9 in B cells in multiple sclerosis. J Neuroimmunol 221(1–2):95–100PubMed
148.
Okada Y, Ochi H, Fujii C, Hashi Y, Hamatani M, Ashida S et al (2018) Signaling via toll-like receptor 4 and CD40 in B cells plays a regulatory role in the pathogenesis of multiple sclerosis through interleukin-10 production. J Autoimmun 88:103–113PubMed
149.
Guo S, Chen Q, Liang X, Mu M, He J, Fang Q et al (2018) Reduced peripheral blood regulatory B cell levels are not associated with the expanded disability status scale score in multiple sclerosis. J Int Med Res 48:3970
150.
Giacomini E, Rizzo F, Etna MP, Cruciani M, Mechelli R, Buscarinu MC et al (2018) Thymosin-alpha1 expands deficient IL-10-producing regulatory B cell subsets in relapsing-remitting multiple sclerosis patients. Mult Scler 24(2):127–139PubMed
151.
Moreno Torres I, Garcia-Merino A (2017) Anti-CD20 monoclonal antibodies in multiple sclerosis. Expert Rev Neurother 17(4):359–371PubMed
152.
Robak T, Robak E (2011) New anti-CD20 monoclonal antibodies for the treatment of B-cell lymphoid malignancies. BioDrugs Clin Immunother, Biopharm Gene Ther 25(1):13–25
153.
Quan C, ZhangBao J, Lu J, Zhao C, Cai T, Wang B et al (2015) The immune balance between memory and regulatory B cells in NMO and the changes of the balance after methylprednisolone or rituximab therapy. J Neuroimmunol 282:45–53PubMed
154.
Sorensen PS, Lisby S, Grove R, Derosier F, Shackelford S, Havrdova E et al (2014) Safety and efficacy of ofatumumab in relapsing-remitting multiple sclerosis: a phase 2 study. Neurology 82(7):573–581PubMed
155.
von Budingen HC, Palanichamy A, Lehmann-Horn K, Michel BA, Zamvil SS (2015) Update on the autoimmune pathology of multiple sclerosis: B-cells as disease-drivers and therapeutic targets. Eur Neurol 73(3–4):238–246
156.
Herbst R, Wang Y, Gallagher S, Mittereder N, Kuta E, Damschroder M et al (2010) B-cell depletion in vitro and in vivo with an afucosylated anti-CD19 antibody. J Pharmacol Exp Ther 335(1):213–222PubMed
157.
Tedder TF (2009) CD19: a promising B cell target for rheumatoid arthritis. Nat Rev Rheumatol 5(10):572–577PubMed
158.
Chen D, Blazek M, Ireland S, Ortega S, Kong X, Meeuwissen A et al (2014) Single dose of glycoengineered anti-CD19 antibody (MEDI551) disrupts experimental autoimmune encephalomyelitis by inhibiting pathogenic adaptive immune responses in the bone marrow and spinal cord while preserving peripheral regulatory mechanisms. J Immunol 193(10):4823–4832PubMed
159.
Chen D, Ireland SJ, Davis LS, Kong X, Stowe AM, Wang Y et al (2016) Autoreactive CD19+CD20- plasma cells contribute to disease severity of experimental autoimmune encephalomyelitis. J Immunol 196(4):1541–1549PubMed
160.
Rotondi M, Molteni M, Leporati P, Capelli V, Marino M, Chiovato L (2017) Autoimmune thyroid diseases in patients treated with alemtuzumab for multiple sclerosis: an example of selective anti-TSH-receptor immune response. Front Endocrinol (Lausanne) 8:254
161.
Simon M, Ipek R, Homola GA, Rovituso DM, Schampel A, Kleinschnitz C et al (2018) Anti-CD52 antibody treatment depletes B cell aggregates in the central nervous system in a mouse model of multiple sclerosis. J Neuroinflammation 15(1):225PubMedPubMedCentral
162.
Liu J, Wang H, Li Y, Shi P, Gong J, Gu L, et al. (2018) Anti-mouse CD52 treatment ameliorates colitis through suppressing Th1/17 mediated inflammation and promoting Tregs differentiation in IL-10 deficient mice. Biol Pharm Bull
163.
Zhang X, Tao Y, Chopra M, Ahn M, Marcus KL, Choudhary N et al (2013) Differential reconstitution of T cell subsets following immunodepleting treatment with alemtuzumab (anti-CD52 monoclonal antibody) in patients with relapsing-remitting multiple sclerosis. J Immunol 191(12):5867–5874PubMed
164.
De Mercanti S, Rolla S, Cucci A, Bardina V, Cocco E, Vladic A et al (2016) Alemtuzumab long-term immunologic effect: Treg suppressor function increases up to 24 months. Neurol Uroimmunol Neuroinflammation 3(1):194
165.
Heidt S, Hester J, Shankar S, Friend PJ, Wood KJ (2012) B cell repopulation after alemtuzumab induction-transient increase in transitional B cells and long-term dominance of naive B cells. Am J Transplant 12(7):1784–1792PubMedPubMedCentral
166.
Baker D, Herrod SS, Alvarez-Gonzalez C, Giovannoni G, Schmierer K (2017) Interpreting lymphocyte reconstitution data from the pivotal phase 3 trials of alemtuzumab. JAMA Neurol 74(8):961–969PubMedPubMedCentral
167.
Dubuisson N, Baker D, Kang AS, Pryce G, Marta M, Visser LH et al (2018) Alemtuzumab depletion failure can occur in multiple sclerosis. Immunology 154(2):253–260PubMedPubMedCentral
168.
Mancuso R, Franciotta D, Rovaris M, Caputo D, Sala A, Hernis A et al (2014) Effects of natalizumab on oligoclonal bands in the cerebrospinal fluid of multiple sclerosis patients: a longitudinal study. Mult Scler. 20(14):1900–1903PubMed
169.
Warnke C, Stettner M, Lehmensiek V, Dehmel T, Mausberg AK, von Geldern G et al (2015) Natalizumab exerts a suppressive effect on surrogates of B cell function in blood and CSF. Mult Scler. 21(8):1036–1044PubMed
170.
Stenner MP, Waschbisch A, Buck D, Doerck S, Einsele H, Toyka KV et al (2008) Effects of natalizumab treatment on Foxp3+T regulatory cells. PLoS ONE 3(10):e3319PubMedPubMedCentral
171.
Putzki N, Baranwal MK, Tettenborn B, Limmroth V, Kreuzfelder E (2010) Effects of natalizumab on circulating B cells, T regulatory cells and natural killer cells. Eur Neurol 63(5):311–317PubMed
172.
Mitsdoerffer M, Kuchroo V, Korn T (2013) Immunology of neuromyelitis optica: a T cell-B cell collaboration. Ann N Y Acad Sci 1283:57–66PubMedPubMedCentral
173.
Li Y, Wang H, Long Y, Lu Z, Hu X (2011) Increased memory Th17 cells in patients with neuromyelitis optica and multiple sclerosis. J Neuroimmunol 234(1–2):155–160PubMed
174.
Dos Passos GR, Sato DK, Becker J, Fujihara K (2016) Th17 cells pathways in multiple sclerosis and neuromyelitis optica spectrum disorders: pathophysiological and therapeutic implications. Mediators Inflamm 2016:5314541PubMedPubMedCentral
175.
Huwiler A, Zangemeister-Wittke U (2018) The sphingosine 1-phosphate receptor modulator fingolimod as a therapeutic agent: recent findings and new perspectives. Pharmacol Ther 185:34–49PubMed
176.
Haas J, Schwarz A, Korporal-Kunke M, Jarius S, Wiendl H, Kieseier BC et al (2015) Fingolimod does not impair T-cell release from the thymus and beneficially affects Treg function in patients with multiple sclerosis. Mult Scler 21(12):1521–1532PubMed
177.
Muls N, Dang HA, Sindic CJ, van Pesch V (2014) Fingolimod increases CD39-expressing regulatory T cells in multiple sclerosis patients. PLoS ONE 9(11):e113025PubMedPubMedCentral
178.
Breuer J, Herich S, Schneider-Hohendorf T, Chasan AI, Wettschureck N, Gross CC, et al (2017) Dual action by fumaric acid esters synergistically reduces adhesion to human endothelium. Mult Scler: 1352458517735189
179.
Chen H, Assmann JC, Krenz A, Rahman M, Grimm M, Karsten CM et al (2014) Hydroxycarboxylic acid receptor 2 mediates dimethyl fumarate’s protective effect in EAE. J Clin Investig 124(5):2188–2192PubMedPubMedCentral
180.
von Glehn F, Dias-Carneiro RPC, Moraes AS, Farias AS, Silva V, Oliveira FTM et al (2018) Dimethyl fumarate downregulates the immune response through the HCA2/GPR109A pathway: implications for the treatment of multiple sclerosis. Mult Scler Relat Disord 23:46–50
181.
Fox RJ, Miller DH, Phillips JT, Hutchinson M, Havrdova E, Kita M et al (2012) Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. New Engl J Med 367(12):1087–1097PubMed
182.
Gold R, Kappos L, Arnold DL, Bar-Or A, Giovannoni G, Selmaj K et al (2012) Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. New Engl J Med 367(12):1098–1107PubMed
183.
Mills EA, Ogrodnik MA, Plave A, Mao-Draayer Y (2018) Emerging understanding of the mechanism of action for dimethyl fumarate in the treatment of multiple sclerosis. Front Neurol 9:5PubMedPubMedCentral
184.
Lundy SK, Wu Q, Wang Q, Dowling CA, Taitano SH, Mao G et al (2016) Dimethyl fumarate treatment of relapsing-remitting multiple sclerosis influences B-cell subsets. Neurol Neuroimmunol Neuroinflammation 3(2):e211
185.
Li R, Rezk A, Ghadiri M, Luessi F, Zipp F, Li H et al (2017) Dimethyl Fumarate Treatment Mediates an Anti-Inflammatory Shift in B Cell Subsets of Patients with Multiple Sclerosis. J Immunol. 198(2):691–698PubMed
186.
Bar-Or A, Pachner A, Menguy-Vacheron F, Kaplan J, Wiendl H (2014) Teriflunomide and its mechanism of action in multiple sclerosis. Drugs 74(6):659–674PubMedPubMedCentral
187.
Ochoa-Reparaz J, Colpitts SL, Kircher C, Kasper EJ, Telesford KM, Begum-Haque S et al (2016) Induction of gut regulatory CD39+T cells by teriflunomide protects against EAE. Neurol Neuroimmunol Neuroinflammation 3(6):e291
188.
Duda PW, Schmied MC, Cook SL, Krieger JI, Hafler DA (2000) Glatiramer acetate (Copaxone) induces degenerate, Th2-polarized immune responses in patients with multiple sclerosis. J Clin Investig 105(7):967–976PubMedPubMedCentral
189.
Dhib-Jalbut S (2002) Mechanisms of action of interferons and glatiramer acetate in multiple sclerosis. Neurology 58(8 Suppl 4):S3–S9PubMed
190.
Racke MK, Lovett-Racke AE, Karandikar NJ (2010) The mechanism of action of glatiramer acetate treatment in multiple sclerosis. Neurology 74(Suppl 1):S25–S30PubMed
191.
Kala M, Rhodes SN, Piao WH, Shi FD, Campagnolo DI, Vollmer TL (2010) B cells from glatiramer acetate-treated mice suppress experimental autoimmune encephalomyelitis. Exp Neurol 221(1):136–145PubMed
192.
Van Kaer L (2011) Glatiramer acetate for treatment of MS: regulatory B cells join the cast of players. Exp Neurol 227(1):19–23PubMed
193.
Ireland SJ, Guzman AA, O’Brien DE, Hughes S, Greenberg B, Flores A et al (2014) The effect of glatiramer acetate therapy on functional properties of B cells from patients with relapsing-remitting multiple sclerosis. JAMA Neurology 71(11):1421–1428PubMedPubMedCentral
194.
Jiang H, Milo R, Swoveland P, Johnson KP, Panitch H, Dhib-Jalbut S (1995) Interferon beta-1b reduces interferon gamma-induced antigen-presenting capacity of human glial and B cells. J Neuroimmunol 61(1):17–25PubMed
195.
Dhib-Jalbut S, Marks S (2010) Interferon-beta mechanisms of action in multiple sclerosis. Neurology 74(Suppl 1):S17–S24PubMed
196.
Schubert RD, Hu Y, Kumar G, Szeto S, Abraham P, Winderl J et al (2015) IFN-beta treatment requires B cells for efficacy in neuroautoimmunity. J Immunol 194(5):2110–2116PubMed
197.
Comabella M, Rio J, Espejo C, Ruiz de Villa M, Al-Zayat H, Nos C et al (2009) Changes in matrix metalloproteinases and their inhibitors during interferon-beta treatment in multiple sclerosis. Clin Immunol 130(2):145–150PubMed
198.
199.
Chalubinski M, Broncel M (2010) Influence of statins on effector and regulatory immune mechanisms and their potential clinical relevance in treating autoimmune disorders. Med Sci Monit Int Med J Exp Clin Res 16(11):245–251
200.
Rodriguez-Perea AL, Montoya CJ, Olek S, Chougnet CA, Velilla PA (2015) Statins increase the frequency of circulating CD4+FOXP3+ regulatory T cells in healthy individuals. J Immunol Res 2015:762506PubMedPubMedCentral
201.
Kim YC, Kim KK, Shevach EM (2010) Simvastatin induces Foxp3+T regulatory cells by modulation of transforming growth factor-beta signal transduction. Immunology 130(4):484–493PubMedPubMedCentral
202.
Peng X, Jin J, Giri S, Montes M, Sujkowski D, Tang Y et al (2006) Immunomodulatory effects of 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitors, potential therapy for relapsing remitting multiple sclerosis. J Neuroimmunol 178(1–2):130–139PubMed
203.
Stuve O, Youssef S, Weber MS, Nessler S, von Budingen HC, Hemmer B et al (2006) Immunomodulatory synergy by combination of atorvastatin and glatiramer acetate in treatment of CNS autoimmunity. J Clin Investig 116(4):1037–1044PubMedPubMedCentral
204.
Palmer MT, Lee YK, Maynard CL, Oliver JR, Bikle DD, Jetten AM et al (2011) Lineage-specific effects of 1,25-dihydroxyvitamin D(3) on the development of effector CD4 T cells. J Biol Chem 286(2):997–1004PubMed
205.
Korf H, Wenes M, Stijlemans B, Takiishi T, Robert S, Miani M et al (2012) 1,25-Dihydroxyvitamin D3 curtails the inflammatory and T cell stimulatory capacity of macrophages through an IL-10-dependent mechanism. Immunobiology 217(12):1292–1300PubMed
206.
Xie Z, Chen J, Zheng C, Wu J, Cheng Y, Zhu S et al (2017) 1,25-dihydroxyvitamin D3 -induced dendritic cells suppress experimental autoimmune encephalomyelitis by increasing proportions of the regulatory lymphocytes and reducing T helper type 1 and type 17 cells. Immunology 152(3):414–424PubMedPubMedCentral
207.
Salzer J, Hallmans G, Nystrom M, Stenlund H, Wadell G, Sundstrom P (2012) Vitamin D as a protective factor in multiple sclerosis. Neurology 79(21):2140–2145PubMed
208.
Soilu-Hanninen M, Laaksonen M, Laitinen I, Eralinna JP, Lilius EM, Mononen I (2008) A longitudinal study of serum 25-hydroxyvitamin D and intact parathyroid hormone levels indicate the importance of vitamin D and calcium homeostasis regulation in multiple sclerosis. J Neurol Neurosurg Psychiatry 79(2):152–157PubMed
209.
Kimball SM, Ursell MR, O’Connor P, Vieth R (2007) Safety of vitamin D3 in adults with multiple sclerosis. Am J Clin Nutr 86(3):645–651PubMed
210.
Cantorna MT, Snyder L, Lin YD, Yang L (2015) Vitamin D and 1,25(OH)2D regulation of T cells. Nutrients 7(4):3011–3021PubMedPubMedCentral
Metadata
Title
Regulatory B and T lymphocytes in multiple sclerosis: friends or foes?
Authors
Georgios K. Vasileiadis
Efthymios Dardiotis
Athanasios Mavropoulos
Zisis Tsouris
Vana Tsimourtou
Dimitrios P. Bogdanos
Lazaros I. Sakkas
Georgios M. Hadjigeorgiou
Publication date
01-12-2018
Publisher
Springer International Publishing
Published in
Autoimmunity Highlights / Issue 1/2018
Print ISSN: 2038-0305
Electronic ISSN: 2038-3274
DOI
https://doi.org/10.1007/s13317-018-0109-x

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