Reciprocal Regulation of Glycolysis-Driven Th17 Pathogenicity and Regulatory T Cell Stability by Cdc42.

ABSTRACT: A balance between Th17 cells and regulatory T cells (Tregs) is important for host immunity and immune tolerance. The underlying molecular mechanisms remain poorly understood. Here we have identified Cdc42 as a central regulator of Th17/Treg balance. Deletion of Cdc42 in T cells enhanced Th17 differentiation but diminished induced Treg differentiation and suppressive function. Treg-specific deletion of Cdc42 decreased natural Tregs but increased effector T cells including Th17 cells. Notably, Cdc42-deficient Th17 cells became pathogenic associated with enhanced glycolysis and Cdc42-deficient Tregs became unstable associated with weakened glycolytic signaling. Inhibition of glycolysis in Cdc42-deficient Th17 cells diminished their pathogenicity and restoration of glycolysis in Cdc42-deficien

SUBMITTER: Kalim KW 

PROVIDER: S-EPMC5860966 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature