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Innate, innate-like and adaptive lymphocytes in the pathogenesis of MS and EAE

Cellular & Molecular Immunology (2019) | Download Citation


Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) in which the immune system damages the protective insulation surrounding the nerve fibers that project from neurons. A hallmark of MS and its animal model, experimental autoimmune encephalomyelitis (EAE), is autoimmunity against proteins of the myelin sheath. Most studies in this field have focused on the roles of CD4+ T lymphocytes, which form part of the adaptive immune system as both mediators and regulators in disease pathogenesis. Consequently, the treatments for MS often target the inflammatory CD4+ T-cell responses. However, many other lymphocyte subsets contribute to the pathophysiology of MS and EAE, and these subsets include CD8+ T cells and B cells of the adaptive immune system, lymphocytes of the innate immune system such as natural killer cells, and subsets of innate-like T and B lymphocytes such as γδ T cells, natural killer T cells, and mucosal-associated invariant T cells. Several of these lymphocyte subsets can act as mediators of CNS inflammation, whereas others exhibit immunoregulatory functions in disease. Importantly, the efficacy of some MS treatments might be mediated in part by effects on lymphocytes other than CD4+ T cells. Here we review the contributions of distinct subsets of lymphocytes on the pathogenesis of MS and EAE, with an emphasis on lymphocytes other than CD4+ T cells. A better understanding of the distinct lymphocyte subsets that contribute to the pathophysiology of MS and its experimental models will inform the development of novel therapeutic approaches.

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The work in the researchers’ lab was supported by grants from the NIH (DK104817 to L.V.K.), the Department of Defense (W81XWH-15-1-0543 to L.V.K.), and the National Multiple Sclerosis Society (60006625 to L.V.K.). J.L.P. was supported by predoctoral NIH training grants (T32HL069765 and T32AR059039).

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  1. Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA

    • Luc Van Kaer
    • , Joshua L. Postoak
    • , Chuan Wang
    • , Guan Yang
    •  & Lan Wu


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