Calcium Signaling Controls Pathogenic Th17 Cell-Mediated Inflammation by Regulating Mitochondrial Function.

ABSTRACT: Pathogenic Th17 cells play important roles in many autoimmune and inflammatory diseases. Their function depends on T cell receptor (TCR) signaling and cytokines that activate signal transducer and activator of transcription 3 (STAT3). TCR engagement activates stromal interaction molecule 1 (STIM1) and calcium (Ca²⁺) influx through Ca²⁺-release-activated Ca²⁺ (CRAC) channels. Here, we show that abolishing STIM1 and Ca²⁺ influx in T cells expressing a hyperactive form of STAT3 (STAT3C) attenuates pathogenic Th17 cell function and inflammation associated with STAT3C expression. Deletion of STIM1 in pathogenic Th17 cells reduces the expression of genes required for mitochondrial function and oxidative phosphorylation (OXPHOS) but enhances reactive ox

SUBMITTER: Kaufmann U 

PROVIDER: S-EPMC6506368 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature