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。
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:22.415
官方网址:https://www.cell.com/cell-metabolism/home
投稿链接:https://www.editorialmanager.com/cell-metabolism/default.aspx