Glucocorticoids (GC) are the mainstay treatment option for inflammatory conditions. Despite the broad usage of GC, the mechanisms by which GC exerts its effects remain elusive. Here, utilizing murine autoimmune and allergic inflammation models, we report that Foxp3⁺ regulatory T (Treg) cells are irreplaceable GC target cells in vivo. Dexamethasone (Dex) administered in the absence of Treg cells completely lost its ability to control inflammation, and the lack of glucocorticoid receptor in Treg cells alone resulted in the loss of therapeutic ability of Dex. Mechanistically, Dex induced miR-342-3p specifically in Treg cells and miR-342-3p directly targeted the mTORC2 component, Rictor. Altering miRNA-342-3p or Rictor expression in Treg cells dysregulated metabolic programming in Treg cells, controlling their regulatory functions in vivo. Our results uncover a previously unknown contribution of Treg cells during glucocorticoid-mediated treatment of inflammation and the underlying mechanisms operated via the Dex-miR-342-Rictor axis.

糖皮质激素 (GC) 是炎症性疾病的主要治疗选择。尽管 GC 被广泛使用，但 GC 发挥其作用的机制仍然难以捉摸。在这里，利用鼠自身免疫和过敏性炎症模型，我们报告 Foxp3 ⁺调节性 T (Treg) 细胞是体内不可替代的 GC 靶细胞. 在没有Treg细胞的情况下给予地塞米松（Dex）完全失去了控制炎症的能力，而单独在Treg细胞中缺乏糖皮质激素受体导致Dex的治疗能力丧失。从机制上讲，Dex 在 Treg 细胞中特异性诱导 miR-342-3p，而 miR-342-3p 直接靶向 mTORC2 成分 Rictor。改变 Treg 细胞中的 miRNA-342-3p 或 Rictor 表达会失调 Treg 细胞中的代谢编程，从而控制它们在体内的调节功能。我们的研究结果揭示了 Treg 细胞在糖皮质激素介导的炎症治疗过程中的一个以前未知的贡献，以及通过 Dex-miR-342-Rictor 轴操作的潜在机制。