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谷胱甘肽限制丝氨酸代谢从而维持调节性T细胞功能
2020-03-26 15:15
来源：小柯机器人

卢森堡卫生研究所Dirk Brenner研究团队的最新工作发现，谷胱甘肽限制丝氨酸代谢从而维持调节性T细胞功能。2020年3月25日，国际知名学术期刊《细胞—代谢》在线发表了这一成果。

研究人员表示，调节性T细胞（Tregs）维持免疫稳态并防止自身免疫。丝氨酸刺激谷胱甘肽（GSH）的合成，并进入效应T细胞（Teff）反应所必需的一碳代谢网络（1CMet）。但是，丝氨酸的功能、与GSH的连锁以及在Treg应激反应中的作用尚不清楚。
 
通过使用Treg特异性敲除谷氨酸半胱氨酸连接酶（Gclc）催化亚基的小鼠，研究人员发现，Treg中GSH的丢失会改变丝氨酸的输入和合成，并且该反馈回路的完整性对于Treg抑制能力至关重要。尽管Gclc敲除不影响Treg分化，但突变小鼠表现出严重的自身免疫性和增强的抗肿瘤反应。Gclc缺陷型Treg表现出丝氨酸代谢、mTOR激活和增殖增加，但FoxP3却下调。在体外和体内细胞丝氨酸的限制恢复了FoxP3表达和Gclc缺陷Tregs的抑制能力。
 
因此，这项工作揭示了GSH在限制丝氨酸可用性以维持Treg功能方面的全新作用。
 
附：英文原文

Title: Glutathione Restricts Serine Metabolism to Preserve Regulatory T Cell Function

Author: Henry Kurniawan, Davide G. Franchina, Luana Guerra, Lynn Bonetti, Leticia Soriano - Baguet, Melanie Grusdat, Lisa Schlicker, Oliver Hunewald, Catherine Dostert, Myriam P. Merz, Carole Binsfeld, Gordon S. Duncan, Sophie Farinelle, Yannic Nonnenmacher, Jillian Haight, Dennis Das Gupta, Anouk Ewen, Rabia Taskesen, Rashi Halder, Ying Chen, Christian Jger, Markus Ollert, Paul Wilmes, Vasilis Vasiliou, Isaac S. Harris, Christiane B. Knobbe-Thomsen, Jonathan D. Turner, Tak W. Mak, Michael Lohoff, Johannes Meiser, Karsten Hiller, Dirk Brenner

Issue&Volume: 2020-03-25

Abstract: Regulatory T cells (Tregs) maintain immune homeostasis and prevent autoimmunity. Serinestimulates glutathione (GSH) synthesis and feeds into the one-carbon metabolic network(1CMet) essential for effector T cell (Teff) responses. However, serine’s functions,linkage to GSH, and role in stress responses in Tregs are unknown. Here, we show,using mice with Treg-specific ablation of the catalytic subunit of glutamate cysteineligase (Gclc), that GSH loss in Tregs alters serine import and synthesis and that the integrityof this feedback loop is critical for Treg suppressive capacity. Although Gclc ablation does not impair Treg differentiation, mutant mice exhibit severe autoimmunityand enhanced anti-tumor responses. Gclc-deficient Tregs show increased serine metabolism, mTOR activation, and proliferationbut downregulated FoxP3. Limitation of cellular serine in vitro and in vivo restores FoxP3 expression and suppressive capacity of Gclc-deficient Tregs. Our work reveals an unexpected role for GSH in restricting serineavailability to preserve Treg functionality.

DOI: 10.1016/j.cmet.2020.03.004

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30119-4

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
官方网址：https://www.cell.com/cell-metabolism/home
投稿链接：https://www.editorialmanager.com/cell-metabolism/default.aspx


本期文章：《细胞—代谢》：Online/在线发表

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