Title | Nutrient mTORC1 signaling underpins regulatory T cell control of immune tolerance. |
Publication Type | Journal Article |
Year of Publication | 2020 |
Authors | Do MH, Wang X, Zhang X, Chou C, Nixon BG, Capistrano KJ, Peng M, Efeyan A, Sabatini DM, Li MO |
Journal | J Exp Med |
Volume | 217 |
Issue | 1 |
Date Published | 2020 Jan 06 |
ISSN | 1540-9538 |
Abstract | Foxp3+ regulatory T (T reg) cells are pivotal regulators of immune tolerance, with T cell receptor (TCR)-driven activated T reg (aT reg) cells playing a central role; yet how TCR signaling propagates to control aT reg cell responses remains poorly understood. Here we show that TCR signaling induces expression of amino acid transporters, and renders amino acid-induced activation of mTORC1 in aT reg cells. T reg cell-specific ablation of the Rag family small GTPases RagA and RagB impairs amino acid-induced mTORC1 signaling, causing defective amino acid anabolism, reduced T reg cell proliferation, and a rampant autoimmune disorder similar in severity to that triggered by T reg cell-specific TCR deficiency. Notably, T reg cells in peripheral tissues, including tumors, are more sensitive to Rag GTPase-dependent nutrient sensing. Ablation of RagA alone impairs T reg cell accumulation in the tumor, resulting in enhanced antitumor immunity. Thus, nutrient mTORC1 signaling is an essential component of TCR-initiated T reg cell reprogramming, and Rag GTPase activities may be titrated to break tumor immune tolerance. |
DOI | 10.1084/jem.20190848 |
Alternate Journal | J. Exp. Med. |
PubMed ID | 31649036 |
Submitted by api_import on December 2, 2019 - 9:43am