科學家揭示糖皮質激素抑炎的機制

科學家揭示糖皮質激素抑炎的機制

作者：

小柯機器人

發布時間：2020/7/25 17:18:25

美國克利夫蘭診所勒納研究所Booki Min團隊發現，糖皮質激素（GC）的抗炎作用是由Foxp3 ⁺調節性T（Treg）細胞通過miR-342依賴性機制產生的。 2020年7月23日，《免疫》在線發表了這一成果。

利用小鼠自身免疫和過敏性炎症模型，研究人員發現Foxp3 ⁺調節性T（Treg）細胞是體內GC特異性靶細胞。在沒有Treg細胞的情況下使用地塞米松（Dex）完全喪失了其控制炎症的能力，在Treg細胞中僅缺失糖皮質激素受體導致Dex的治療功能喪失。

從機理上講，Dex在Treg細胞中特異性誘導miR-342-3p，而miR-342-3p直接靶向mTORC2組分Rictor。改變Treg細胞中miRNA-342-3p或Rictor的表達會異常調控Treg細胞中的代謝途徑，從而調控它們在體內的調節功能。

該研究結果揭示了糖皮質激素介導的炎症治療過程中Treg細胞的未知功能，以及通過Dex-miR-342-Rictor軸起作用的潛在機制。

研究人員表示，GC是治療炎性疾病的首選藥物。儘管GC已廣泛使用，但GC發揮作用的機制仍然未知。

附：英文原文

Title: Anti-inflammatory Roles of Glucocorticoids Are Mediated by Foxp3+ Regulatory T Cells via a miR-342-Dependent Mechanism

Author: Dongkyun Kim, Quang Tam Nguyen, Juyeun Lee, Sung Hwan Lee, Allison 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

Issue&Volume: 2020-07-23

Abstract: Glucocorticoids (GC) are the mainstay treatment option for inflammatory conditions.Despite the broad usage of GC, the mechanisms by which GC exerts its effects remainelusive. Here, utilizing murine autoimmune and allergic inflammation models, we reportthat Foxp3+ regulatory T (Treg) cells are irreplaceable GC target cells in vivo. Dexamethasone (Dex) administered in the absence of Treg cells completely lost itsability to control inflammation, and the lack of glucocorticoid receptor in Treg cellsalone resulted in the loss of therapeutic ability of Dex. Mechanistically, Dex inducedmiR-342-3p specifically in Treg cells and miR-342-3p directly targeted the mTORC2component, Rictor. Altering miRNA-342-3p or Rictor expression in Treg cells dysregulatedmetabolic programming in Treg cells, controlling their regulatory functions in vivo. Our results uncover a previously unknown contribution of Treg cells during glucocorticoid-mediatedtreatment of inflammation and the underlying mechanisms operated via the Dex-miR-342-Rictoraxis.

DOI: 10.1016/j.immuni.2020.07.002

Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30282-X