Innate, innate-like and adaptive lymphocytes in the pathogenesis of MS and EAE
Open accessAbstract
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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In multiple sclerosis, the number of MAIT cells is elevated, with MAIT cells producing higher levels of pro-inflammatory cytokines, concomitant with an increase in MR1 expression.
“Of note, in multiple sclerosis (MS), the number of MAIT cells is elevated, with MAIT cells producing a higher level of pro-inflammatory cytokines, concomitant with an increase in MR1 expression [10, 13].”
From Control of the temporal development of Alzheimer’s disease pathology by the MR1/MAIT cell axis (2023) · cites this paper as [10]
The “INNATE-LIKE T AND B CELLS” section reports increased IL-17 production by MAIT cells in MS, supporting the cytokine claim in that specific respect. It says most studies found fewer circulating MAIT cells, although one found more, and it does not report increased MR1 expression. Page numbers were not available in our copy. (LLM, conf=0.90)
Experimental — accuracy not yet measuredMR1 presents microbial vitamin B-derived metabolites to an innate T cell subpopulation called mucosal-associated invariant T (MAIT) cells.
“The MHC class I-related molecule MR1 [9], presents microbial vitamin B-derived metabolites to an innate T cell subpopulation called mucosal-associated invariant T (MAIT) cells [10, 11].”
From Control of the temporal development of Alzheimer’s disease pathology by the MR1/MAIT cell axis (2023) · cites this paper as [10]
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Innate or adaptive immunity? The example of natural killer cells
Vivier, E., Raulet, D. H., Moretta, A., Caligiuri, M. A., Zitvogel, L., Lanier, L. L., Yokoyama, W. M., & Ugolini, S. (2011) · Science · doi:10.1126/science.1198687 · Cited by 2,824 · see citing works
Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
The International Multiple Sclerosis Genetics Consortium & The Wellcome Trust Case Control Consortium 2 (2011) · Nature · doi:10.1038/nature10251 · Cited by 2,697 · see citing works
Immunology of multiple sclerosis
Sospedra, M., & Martin, R. (2005) · Annual Review of Immunology · doi:10.1146/annurev.immunol.23.021704.115707 · Cited by 2,149 · see citing works
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- Authors
- Van Kaer, L., Postoak, J. L., Wang, C., Yang, G., & Wu, L.
- Affiliations
- Vanderbilt University (US)
- Venue
- Cellular & Molecular Immunology
- Published
- 2019-03-15
- Volume
- 16
- Issue
- 6
- Pages
- 531-539
- ISSN
- 1672-7681 (ISSN-L)
- 2042-0226
- PMC
- PMC6804597
- OpenAlex
- W2922505501
- Cited by
- 148
- References
- 3
- Citations by year
- 2026: 15 · 2025: 13 · 2024: 26 · 2023: 26 · 2022: 17 · 2021: 28 · 2020: 17 · 2019: 6
- FWCI
- 2.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cellular and Molecular Immunology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (DK104817)
- U.S. Department of Defense (W81XWH-15-1-0543)
- National Multiple Sclerosis Society (60006625)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- multiple sclerosis, experimental autoimmune encephalomyelitis, innate lymphoid cells, innate-like lymphocytes, CD8+ T cells, B cells, natural killer cells, γδ T cells, NKT cells, mucosal-associated invariant T cells, myelin autoimmunity, neuroinflammation, immune regulation, pathogenesis
- MeSH terms
- Animals, Disease Models, Animal, Encephalomyelitis, Autoimmune, Experimental, Humans, Immunity, Innate, Multiple Sclerosis, T-Lymphocytes, Adaptive Immunity
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