Nutrient mTORC1 signaling underpins regulatory T cell control of immune tolerance Journal Article
| Authors: | Do, M. H.; Wang, X.; Zhang, X.; Chou, C.; Nixon, B. G.; Capistrano, K. J.; Peng, M.; Efeyan, A.; Sabatini, D. M.; Li, M. O. |
| Article Title: | Nutrient mTORC1 signaling underpins regulatory T cell control of immune tolerance |
| 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. © 2019 Do et al. |
| Journal Title: | Journal of Experimental Medicine |
| Volume: | 217 |
| Issue: | 1 |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Date Published: | 2020-01-06 |
| Start Page: | e20190848 |
| Language: | English |
| DOI: | 10.1084/jem.20190848 |
| PUBMED: | 31649036 |
| PROVIDER: | scopus |
| PMCID: | PMC7037250 |
| DOI/URL: | |
| Notes: | Source: Scopus |
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