Department of Biotechnology
inStem (Institute for Stem Cell Science and Regenerative Medicine)

Methionine uptake via the SLC43A2 transporter is essential for regulatory T-cell survival.

Publication Type

Journal Article

Date of Publication

September 9, 2022

Journal

Life science alliance

Volume/Issue

5/12

ISSN

2575-1077

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.

Alternate Journal

Life Sci Alliance

PubMed ID

36260753

PubMed Central ID

PMC9463494

Authors

Neetu Saini
Afsana Naaz
Shree Padma Metur
Pinki Gahlot
Adhish Walvekar
Anupam Dutta
Umamaheswari Davathamizhan
Apurva Sarin
Sunil Laxman

Keywords

Methionine
Interleukin-2
Racemethionine
Solute Carrier Proteins
T-Lymphocytes, Regulatory