Article (Scientific journals)
Glutathione Restricts Serine Metabolism to Preserve Regulatory T Cell Function
Kurniawan, Henry; Franchina, Davide G.; Guerra, Luana et al.
2020In Cell Metabolism, 31 (5), p. 920--936.e7
Peer reviewed
 

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Keywords :
Treg; ROS; serine metabolism; glutathione; glutamate cysteine ligase; one carbon metabolism; FoxP3; autoimmunity; cancer; diet
Abstract :
[en] Regulatory T cells (Tregs) maintain immune homeostasis and prevent autoimmunity. Serine stimulates 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 cysteine ligase ( Gclc), that GSH loss in Tregs alters serine import and synthesis and that the integrity of this feedback loop is critical for Treg suppressive capacity. Although Gclc ablation does not impair Treg differentiation, mutant mice exhibit severe autoimmunity and enhanced anti-tumor responses. Gclc-deficient Tregs show increased serine metabolism, mTOR activation, and proliferation but 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 serine availability to preserve Treg functionality.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Kurniawan, Henry
Franchina, Davide G.
Guerra, Luana ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Bonetti, Lynn ;  University of Luxembourg > Faculty of Science, Technology and Medecine (FSTM)
- Baguet, Leticia Soriano
Grusdat, Melanie
Schlicker, Lisa
Hunewald, Oliver
Dostert, Catherine
Merz, Myriam P.
Binsfeld, Carole
Duncan, Gordon S.
Farinelle, Sophie ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Nonnenmacher, Yannic
Haight, Jillian
Das Gupta, Dennis
Ewen, Anouk
Taskesen, Rabia
Halder, Rashi ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Chen, Ying
Jäger, Christian  ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Ollert, Markus
Wilmes, Paul ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Vasiliou, Vasilis
Harris, Isaac S.
Knobbe-Thomsen, Christiane B.
Turner, Jonathan ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC)
Mak, Tak W.
Lohoff, Michael
Meiser, Johannes ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Hiller, Karsten
Brenner, Dirk  ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC)
More authors (22 more) Less
External co-authors :
yes
Language :
English
Title :
Glutathione Restricts Serine Metabolism to Preserve Regulatory T Cell Function
Publication date :
05 May 2020
Journal title :
Cell Metabolism
ISSN :
1550-4131
Volume :
31
Issue :
5
Pages :
920--936.e7
Peer reviewed :
Peer reviewed
Focus Area :
Systems Biomedicine
Available on ORBilu :
since 13 July 2020

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