Cited by 39Multiple Sclerosis Research StudiesPsoriasis: Treatment and PathogenesisT-cell and B-cell Immunology

Male sex chromosomal complement exacerbates the pathogenicity of Th17 cells in a chronic model of central nervous system autoimmunity

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Doss, Prenitha Mercy Ignatius Arokia, Umair, Muhammad, Baillargeon, Joanie, Fazazi, Reda, Fudge, Neva, Akbar, Irshad, Yeola, Asmita Pradeep, Williams, John B. +11 more·2021·Cell Reports

Abstract

Sex differences in multiple sclerosis (MS) incidence and severity have long been recognized. However, the underlying cellular and molecular mechanisms for why male sex is associated with more aggressive disease remain poorly defined. Using a T cell adoptive transfer model of chronic experimental autoimmune encephalomyelitis (EAE), we find that male Th17 cells induce disease of increased severity relative to female Th17 cells, irrespective of whether transferred to male or female recipients. Throughout the disease course, a greater frequency of male Th17 cells produce IFNγ, a hallmark of pathogenic Th17 responses. Intriguingly, XY chromosomal complement increases the pathogenicity of male Th17 cells. An X-linked immune regulator, Jarid1c, is downregulated in pathogenic male murine Th17 cells, and functional experiments reveal that it represses the severity of Th17-mediated EAE. Furthermore, Jarid1c expression is downregulated in CD4 + T cells from MS-affected individuals. Our data indicate that male sex chromosomal complement critically regulates Th17 cell pathogenicity.

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Crossref · 10.1016/j.celrep.2021.108833

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  • Dysregulation of microglial functions is associated with several health concerns that often show sex prevalences, including Alzheimer's disease (more prevalent among females), Parkinson's disease (more male-prevalent), and various other neurodevelopmental, neuropsychiatric and neurodegenerative disorders.

    “Dysregulation of microglial functions is associated with several health concerns that often show sex prevalences, not only affecting Alzheimer’s disease, which shows more prevalence among females, and Parkinson’s disease, more male-prevalent, but also including various other neurodevelopmental, neuropsychiatric and neurodegenerative disorders [38–43].”

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Authors
Doss, P. M. I. A., Umair, M., Baillargeon, J., Fazazi, R., Fudge, N., Akbar, I., Yeola, A. P., Williams, J. B., Leclercq, M., Joly-Beauparlant, C., Beauchemin, P., Ruda, G. F., Alpaugh, M., Anderson, A. C., Brennan, P. E., Droit, A., Lassmann, H., Moore, C. S., & Rangachari, M.
Affiliations
  • Centre hospitalier de l'Université Laval (CA)
  • Memorial University of Newfoundland (CA)
  • Université Laval (CA)
  • University of Oxford (GB)
  • Brigham and Women's Hospital (US)
  • Medical University of Vienna (AT)
Corresponding author
Rangachari, Manu
Venue
Cell Reports
Publisher
Elsevier BV
Published
2021-03
Volume
34
Issue
10
Pages
108833
ISSN
2211-1247 (ISSN-L)
OpenAlex
W3135046858
Cited by
39
References
98
Citations by year
2026: 8 · 2025: 3 · 2024: 3 · 2023: 10 · 2022: 11 · 2021: 3 · 2019: 1
FWCI
4.50
Type
journal article
Language
en
Open access
Locations
  • Cell Reports (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Canadian Institutes of Health Research
  • Multiple Sclerosis Society of Canada
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords
sex differences, multiple sclerosis, Th17 cells, experimental autoimmune encephalitis, JARID1C, interferon-gamma, CD4+ T cells, central nervous system autoimmunity, disease severity
MeSH terms
Animals, Disease Models, Animal, Encephalomyelitis, Autoimmune, Experimental, Female, Humans, Interferon-gamma, Male, Mice, Transgenic, Middle Aged, Multiple Sclerosis, Severity of Illness Index, Sex Chromosomes, CD4-Positive T-Lymphocytes, Down-Regulation, Autoimmunity, Mice, Inbred NOD, Mice, Histone Demethylases, Nuclear Receptor Subfamily 1, Group F, Member 3, Th17 Cells

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