| First Author | Do MH | Year | 2020 |
| Journal | J Exp Med | Volume | 217 |
| Issue | 1 | PubMed ID | 31649036 |
| Mgi Jnum | J:285445 | Mgi Id | MGI:6392650 |
| Doi | 10.1084/jem.20190848 | Citation | Do MH, et al. (2020) Nutrient mTORC1 signaling underpins regulatory T cell control of immune tolerance. J Exp Med 217(1) |
| abstractText | 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. |
