GSE136969
Foxp3+ regulatory T cells mediate glucocorticoid-induced treatment via a miR342-dependent metabolic programming
Glucocorticoids (GC) are the mainstay treatment option for acute and chronic inflammatory conditions including autoimmune and allergic diseases. Despite the broad usage of GC in managing inflammatory conditions, the mechanisms by which GC exerts its immune modulatory functions remain poorly understood. Here, utilizing murine autoimmune and allergic inflammation models we report that Foxp3+ regulatory T (Treg) cells are the primary target cells of GC necessary for its anti-inflammatory functions. Dexamethasone (Dex) administered in the absence of Tregs was unable to inhibit inflammatory responses, and adoptive Treg cell transfer restored the control. Glucocorticoid receptor (GR) expression in Treg cells was essential, suggesting a direct involvement of Treg cells. Genome-wide RNA sequencing analysis uncovered a unique Dex-induced gene signature in Treg cells. miRNA-342-3p was induced by Dex treatment only in inducible Treg cells, and mTORC2 protein, Rictor, expression was directly controlled by miRNA-342. Modulation of miRNA-342 expression level directly controlled Treg cell suppressive functions by altering metabolic profiles. Collectively, our results uncover for the first time a novel pathway by which GC interferes with inflammatory responses via miR-342-dependent metabolic control in Treg cells. Overall design: Three samples for each group. Vehicle-treated samples were used as control for the comparison.