Methionine uptake via SLC43A2 transporter is essential for regulatory T lymphocyte survival

Abstract

AbstractIt is increasingly clear that cell death, survival or growth decisions of T lymphocyte subsets depend on interplay between cytokine-dependent and metabolic processes. What the metabolic requirements of T regulatory cells (Tregs) for their survival are, and how these requirements are satisfied remain to be fully understood. In this study, we identified a necessary requirement of methionine uptake and utilization for Tregs survival upon interleukin 2 (IL-2) deprivation. Activated Tregs have high methionine uptake and consumption to S-adenosyl methionine (SAM) and S-adenosyl homocysteine (SAH). This methionine uptake is essential for Tregs survival, and is regulated by Notch1 activity. Notch1 controls the expression of the solute carrier protein SLC43A2 transporter during IL-2 deprivation. SLC43A2 is necessary for sufficient methionine uptake, and determines Tregs viability upon IL-2 withdrawal. Collectively, we identify a specifically regulated mechanism of methionine import in Tregs that is necessary for the survival of these cells. This highlights the need for methionine availability and metabolism in contextually regulating cell death in an immunosuppressive population of T lymphocytes.