The deacetylase SIRT2 contributes to autoimmune disease pathogenesis by modulating IL-17A and IL-2 transcription.

ABSTRACT: Aberrant IL-17A expression together with reduced IL-2 production by effector CD4⁺ T cells contributes to the pathogenesis of systemic lupus erythematosus (SLE). Here, we report that Sirtuin 2 (SIRT2), a member of the family of NAD⁺-dependent histone deacetylases, suppresses IL-2 production by CD4⁺ T cells while promoting their differentiation into Th17 cells. Mechanistically, we show that SIRT2 is responsible for the deacetylation of p70S6K, activation of the mTORC1/HIF-1α/RORγt pathway and induction of Th17-cell differentiation. Additionally, SIRT2 was shown to be responsible for the deacetylation of c-Jun and histones at the Il-2 gene, resulting in decreased IL-2 production. We found that the transcription factor inducible cAMP early repressor (ICER), whi

SUBMITTER: Hisada R 

PROVIDER: S-EPMC9151795 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature