生物
FOXP3型
糖皮质激素
糖皮质激素受体
Treg细胞
地塞米松
免疫学
炎症
体内
细胞生物学
免疫系统
调节性T细胞
癌症研究
机制(生物学)
T细胞
白细胞介素2受体
内分泌学
遗传学
认识论
哲学
作者
Dongkyun Kim,Quan Nguyen,Juyeun Lee,Sung Hwan Lee,Allison J. Janocha,Sohee Kim,Hongnga T. Le,Nina Dvorina,Kelly Weiss,Mark J. Cameron,Kewal Asosingh,Serpil C. Erzurum,William M. Baldwin,Ju Seog Lee,Booki Min
出处
期刊:Immunity
[Elsevier]
日期:2020-09-01
卷期号:53 (3): 581-596.e5
被引量:63
标识
DOI:10.1016/j.immuni.2020.07.002
摘要
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.
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