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科学家揭示糖皮质激素抑炎的机制
作者:小柯机器人 发布时间:2020/7/25 17:18:25

美国克利夫兰诊所勒纳研究所Booki Min团队发现,糖皮质激素(GC)的抗炎作用是由Foxp3 +调节性T(Treg)细胞通过miR-342依赖性机制产生的。 2020年7月23日,《免疫》在线发表了这一成果。

利用小鼠自身免疫和过敏性炎症模型,研究人员发现Foxp3 +调节性T(Treg)细胞是体内GC特异性靶细胞。在没有Treg细胞的情况下使用地塞米松(Dex)完全丧失了其控制炎症的能力,在Treg细胞中仅缺失糖皮质激素受体导致Dex的治疗功能丧失。

从机理上讲,Dex在Treg细胞中特异性诱导miR-342-3p,而miR-342-3p直接靶向mTORC2组分Rictor。改变Treg细胞中miRNA-342-3p或Rictor的表达会异常调控Treg细胞中的代谢途径,从而调控它们在体内的调节功能。

该研究结果揭示了糖皮质激素介导的炎症治疗过程中Treg细胞的未知功能,以及通过Dex-miR-342-Rictor轴起作用的潜在机制。

研究人员表示,GC是治疗炎性疾病的首选药物。尽管GC已广泛使用,但GC发挥作用的机制仍然未知。

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

期刊信息

Immunity:《免疫》,创刊于1994年。隶属于细胞出版社,最新if:21.522
官方网址:https://www.cell.com/immunity/home
投稿链接:https://www.editorialmanager.com/immunity/default.aspx