GLK-IKKβ signaling induces dimerization and translocation of the AhR-RORγt complex in IL-17A induction and autoimmune disease.

ABSTRACT: Retinoic-acid-receptor-related orphan nuclear receptor γt (RORγt) controls the transcription of interleukin-17A (IL-17A), which plays critical roles in the pathogenesis of autoimmune diseases. Severity of several human autoimmune diseases is correlated with frequencies of germinal center kinase-like kinase (GLK) (also known as MAP4K3)-overexpressing T cells; however, the mechanism of GLK overexpression-induced autoimmunity remains unclear. We report the signal transduction converging on aryl hydrocarbon receptor (AhR)-RORγt interaction to activate transcription of the IL-17A gene in T cells. T cell-specific GLK transgenic mice spontaneously developed autoimmune diseases with selective induction of IL-17A in T cells. In GLK transgenic T cells, protein kinase Cθ (PKCθ) phosphorylated AhR at

SUBMITTER: Chuang HC 

PROVIDER: S-EPMC6135549 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature