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Decoupling the role of RORgt in the differentiation and effector function of Th17 cells

ABSTRACT: RORgt is known to instruct the differentiation of Th17 cells that mediate the pathogenesis of autoimmune diseases. However, it remains unknown whether RORgt plays a distinct role in the differentiation and effector function of Th17 cells. Here we show that mutation of RORgt lysine 256, a ubiquitination site, to arginine (K256R) separates the RORgt role in these two functions. Preventing ubiquitination at K256 via arginine substitution does not affect RORgt-dependent thymocyte development and Th17 differentiation in vitro and in vivo, however, greatly impaired the pathogenesis of Th17 cell-mediated experimental autoimmune encephalomyelitis (EAE). Mechanistically, K256R mutation impairs RORgt to bind to and activate Runx1 expression critical for Th17-mediated EAE. Thus, RORgt regulates the effector function of Th17 cells in addition to Th17 differentiation. This work informs the development of RORgt-based therapies that specifically target the effector function of Th17 cells responsible for autoimmunity.

ORGANISM(S): Mus musculus

PROVIDER: GSE211509 | GEO | 2022/10/26

REPOSITORIES: GEO

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Decoupling the role of RORγt in the differentiation and effector function of Th17 cells

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Decoupling the role of RORgt in the differentiation and effector function of Th17 cells

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