Reference : Glutathione Restricts Serine Metabolism to Preserve Regulatory T Cell Function
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Systems Biomedicine
http://hdl.handle.net/10993/43831
Glutathione Restricts Serine Metabolism to Preserve Regulatory T Cell Function
English
Kurniawan, Henry [> >]
Franchina, Davide G. [> >]
Guerra, Luana mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Bonetti, Lynn [> >]
- Baguet, Leticia Soriano [> >]
Grusdat, Melanie [> >]
Schlicker, Lisa [> >]
Hunewald, Oliver [> >]
Dostert, Catherine [> >]
Merz, Myriam P. [> >]
Binsfeld, Carole [> >]
Duncan, Gordon S. [> >]
Farinelle, Sophie mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Nonnenmacher, Yannic [> >]
Haight, Jillian [> >]
Das Gupta, Dennis [> >]
Ewen, Anouk [> >]
Taskesen, Rabia [> >]
Halder, Rashi mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Chen, Ying [> >]
Jäger, Christian mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Ollert, Markus [> >]
Wilmes, Paul mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Vasiliou, Vasilis [> >]
Harris, Isaac S. [> >]
Knobbe-Thomsen, Christiane B. [> >]
Turner, Jonathan mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) >]
Mak, Tak W. [> >]
Lohoff, Michael [> >]
Meiser, Johannes mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Hiller, Karsten [> >]
Brenner, Dirk mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) >]
5-May-2020
Cell Metabolism
31
5
920--936.e7
Yes (verified by ORBilu)
International
15504131
[en] Treg ; ROS ; serine metabolism ; glutathione ; glutamate cysteine ligase ; one carbon metabolism ; FoxP3 ; autoimmunity ; cancer ; diet
[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.
http://hdl.handle.net/10993/43831
10.1016/j.cmet.2020.03.004
https://linkinghub.elsevier.com/retrieve/pii/S1550413120301194

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