Stress-Induced Glucocorticoids Exacerbate Inflammation and Autoimmunity by Promoting the Differentiation and Function of Th17 Cells [hTh17_RNAseq]
Stress elicits inflammatory and autoimmune diseases while concurrently triggering the production of glucocorticoids (GCs), renowned for their anti-inflammatory effects. In addition, IL-17-producing helper T (Th17) cells are pivotal in initiating inflammation and certain autoimmune disorders. However, whether stress-induced GCs exacerbate inflammatory and autoimmune diseases through Th17 cells remains elusive. Here, we show that GCs facilitate the differentiation and survival of Th17 cells in mice. GCs inhibit the expression of TCF1, a negative regulator of Th17 cell differentiation, thereby increasing pathogenic TCF1low Th17 cells characterized by high glycolytic activity. Remarkably, mice lacking the glucocorticoid receptor (GR), specifically in ?? T cells, manifest less severe experimental autoimmune encephalomyelitis (EAE) and inflammatory colitis. Moreover, stress-induced GCs augment the population of Th17 cells, intensify their IL-17 production, and provoke neutrophil recruitment, resulting in severe inflammation and substantial weight loss in the colitis model. This study demonstrates that stress-induced GCs exacerbate inflammation and autoimmunity by fostering Th17 cell differentiation. Overall design: Transcriptional profiling of CCR6+ CD4 T cells isolated from human CD4 T cells cultured under Th17-differentiation condition (IL-6+TGFb+IL-23)