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- W4313369075 abstract "Abstract Glucocorticoid (GC) is a class of steroid hormones with profound immunosuppressive and anti-inflammatory properties that is widely used as the first-line treatment option in chronic inflammatory conditions such as autoimmunity. Despite the broad usage, its working mechanisms remain largely unclear. Herein, we report that Foxp3+ CD4+ regulatory T cells (Tregs) play an irreplaceable role during GC-mediated treatment of experimental autoimmune encephalomyelitis (EAE), a murine autoimmune inflammation model in the central nervous system that resembles multiple sclerosis in human. Dexamethasone (Dex) administered at the disease onset or ongoing disease was unable to suppress EAE without Tregs, while adoptive transfer of Tregs restored Dex effects. Glucocorticoid receptor (GR) expression in Tregs was essential for Dex effects, suggesting that GC directly acts on Tregs. From RNA sequencing analysis we found that Dex treatment induced miR-342 expression only in Tregs but not in effector T cells. We also found that miR-342 targets the Rictor, a subunit of the mTORC2 complex. Inhibiting Dex-induced miR-342 expression in Tregs not only restored Rictor expression but also interfered with Treg-mediated suppression of EAE even with Dex treatment. While Dex-stimulated Tregs displayed robust oxidative phosphorylation rather than glycolysis as the energy source, miR-342 inhibition in Tregs reversed metabolic program to robust glycolysis. Taken together, this is the first report demonstrating that the miR-342-Rictor axis may represent a novel mechanism by which GC controls inflammation by metabolic programming in Tregs." @default.
- W4313369075 created "2023-01-06" @default.
- W4313369075 creator A5020575520 @default.
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- W4313369075 date "2020-05-01" @default.
- W4313369075 modified "2023-09-27" @default.
- W4313369075 title "Foxp3+ regulatory T cells play an indispensable role during glucocorticoid-induced treatment of autoimmune inflammation" @default.
- W4313369075 doi "https://doi.org/10.4049/jimmunol.204.supp.143.7" @default.
- W4313369075 hasPublicationYear "2020" @default.
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