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

Authors :
Doss, Prenitha Mercy Ignatius Arokia
Umair, Muhammad
Baillargeon, Joanie
Fazazi, Reda
Fudge, Neva
Akbar, Irshad
Yeola, Asmita Pradeep
Williams, John B.
Leclercq, Mickael
Joly-Beauparlant, Charles
Beauchemin, Philippe
Ruda, Gian Filipo
Alpaugh, Melanie
Anderson, Ana C.
Brennan, Paul E.
Droit, Arnaud
Lassmann, Hans
Moore, Craig S.
Rangachari, Manu
Source :
Cell Reports; March 2021, Vol. 34 Issue: 10
Publication Year :
2021

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, Jarid1cexpression is downregulated in CD4+T cells from MS-affected individuals. Our data indicate that male sex chromosomal complement critically regulates Th17 cell pathogenicity.

Details

Language :
English
ISSN :
22111247
Volume :
34
Issue :
10
Database :
Supplemental Index
Journal :
Cell Reports
Publication Type :
Periodical
Accession number :
ejs55509790
Full Text :
https://doi.org/10.1016/j.celrep.2021.108833