TitleMethionine uptake via the SLC43A2 transporter is essential for regulatory T-cell survival.
Publication TypeJournal Article
Year of Publication2022
AuthorsSaini N, Naaz A, Metur SPadma, Gahlot P, Walvekar A, Dutta A, Davathamizhan U, Sarin A, Laxman S
JournalLife Sci Alliance
Volume5
Issue12
Date Published2022 Sep 09
ISSN2575-1077
KeywordsInterleukin-2, Methionine, Racemethionine, Solute Carrier Proteins, T-Lymphocytes, Regulatory
Abstract

Cell death, survival, or growth decisions in T-cell subsets depend on interplay between cytokine-dependent and metabolic processes. The metabolic requirements of T-regulatory cells (Tregs) for their survival and how these are satisfied remain unclear. Herein, we identified a necessary requirement of methionine uptake and usage for Tregs survival upon IL-2 deprivation. Activated Tregs have high methionine uptake and usage to S-adenosyl methionine, and this uptake is essential for Tregs survival in conditions of IL-2 deprivation. We identify a solute carrier protein SLC43A2 transporter, regulated in a Notch1-dependent manner that is necessary for this methionine uptake and Tregs viability. Collectively, we uncover a specifically regulated mechanism of methionine import in Tregs that is required for cells to adapt to cytokine withdrawal. We highlight the need for methionine availability and metabolism in contextually regulating cell death in this immunosuppressive population of T cells.

DOI10.26508/lsa.202201663
Alternate JournalLife Sci Alliance
PubMed ID36260753
PubMed Central IDPMC9463494

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