Male sex chromosomal complement exacerbates the pathogenicity of Th17 cells in a chronic model of central nervous system autoimmunity.
Animals
Autoimmunity
CD4-Positive T-Lymphocytes
/ cytology
Disease Models, Animal
Down-Regulation
Encephalomyelitis, Autoimmune, Experimental
/ immunology
Female
Histone Demethylases
/ genetics
Humans
Interferon-gamma
/ metabolism
Male
Mice
Mice, Inbred NOD
Mice, Transgenic
Middle Aged
Multiple Sclerosis
/ immunology
Nuclear Receptor Subfamily 1, Group F, Member 3
/ metabolism
Severity of Illness Index
Sex Chromosomes
/ genetics
Th17 Cells
/ cytology
IFNγ
IL-17
Jarid1c
Th17
experimental autoimmune encephalomyelitis
four core genotypes
multiple sclerosis
non-obese diabetic
progressive multiple sclerosis
sex chromosome complement
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
09 03 2021
09 03 2021
Historique:
received:
17
06
2019
revised:
13
12
2020
accepted:
16
02
2021
entrez:
10
3
2021
pubmed:
11
3
2021
medline:
27
1
2022
Statut:
ppublish
Résumé
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
Identifiants
pubmed: 33691111
pii: S2211-1247(21)00147-9
doi: 10.1016/j.celrep.2021.108833
pii:
doi:
Substances chimiques
Nuclear Receptor Subfamily 1, Group F, Member 3
0
Rorc protein, mouse
0
Interferon-gamma
82115-62-6
Histone Demethylases
EC 1.14.11.-
Kdm5c protein, mouse
EC 1.14.11.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
108833Subventions
Organisme : CIHR
Pays : Canada
Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests M.R. has received speaker honoraria from Boehringer-Ingelheim GmbH, EMD Serono Canada, F. Hoffmann-La Roche, and Biogen Canada and has a research contract with Remedy Pharmaceuticals. These interests are unrelated to the present work.