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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 research bulletin

Publication Date

08/2023

Addresses

axe Neurosciences, Centre de recherche du CHU de Québec-Université Laval, Québec QC Canada.