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T cell-driven autoimmune responses are subject to striking sex-dependent effects. While the contributions of sex hormones are well-understood, those of sex chromosomes are meeting with increased appreciation. Here, we outline what is known about the contribution of sex chromosome-linked factors to experimental autoimmune encephalomyelitis (EAE), a mouse model that recapitulates many of the T cell-driven mechanisms of multiple sclerosis (MS) pathology. Particular attention is paid to the KDM family of histone demethylases, several of which - KDM5C, KDM5D and KDM6A - are sex chromosome encoded. Finally, we provide evidence that functional inhibition of KDM5 molecules can suppress interferon (IFN)γ production from murine male effector T cells, and that an increased ratio of inflammatory Kdm6a to immunomodulatory Kdm5c transcript is observed in T helper 17 (Th17) cells from women with the autoimmune disorder ankylosing spondylitis (AS). Histone lysine demethlyases thus represent intriguing targets for the treatment of T cell-driven autoimmune disorders.

Original publication

DOI

10.1016/j.brainresbull.2023.110748

Type

Journal article

Journal

Brain Res Bull

Publication Date

01/10/2023

Volume

202

Keywords

Experimental autoimmune encephalomyelitis, KDM5c, KDM6A, Multiple sclerosis, Sex differences, Th17 cell, Animals, Female, Humans, Male, Mice, Autoimmunity, Central Nervous System, Encephalomyelitis, Autoimmune, Experimental, Histone Demethylases, Minor Histocompatibility Antigens, T-Lymphocytes