| First Author | Yu X | Year | 2018 |
| Journal | J Exp Med | Volume | 215 |
| Issue | 9 | Pages | 2463-2476 |
| PubMed ID | 30115741 | Mgi Jnum | J:266093 |
| Mgi Id | MGI:6201857 | Doi | 10.1084/jem.20180397 |
| Citation | Yu X, et al. (2018) Metabolic control of regulatory T cell stability and function by TRAF3IP3 at the lysosome. J Exp Med 215(9):2463-2476 |
| abstractText | Metabolic programs are crucial for regulatory T (T reg) cell stability and function, but the underlying mechanisms that regulate T reg cell metabolism are elusive. Here, we report that lysosomal TRAF3IP3 acts as a pivotal regulator in the maintenance of T reg cell metabolic fitness. T reg-specific deletion of Traf3ip3 impairs T reg cell function, causing the development of inflammatory disorders and stronger antitumor T cell responses in mice. Excessive mechanistic target of rapamycin complex 1 (mTORC1)-mediated hyper-glycolytic metabolism is responsible for the instability of TRAF3IP3-deficient T reg cells. Mechanistically, TRAF3IP3 restricts mTORC1 signaling by recruiting the serine-threonine phosphatase catalytic subunit (PP2Ac) to the lysosome, thereby facilitating the interaction of PP2Ac with the mTORC1 component Raptor. Our results define TRAF3IP3 as a metabolic regulator in T reg cell stability and function and suggest a lysosome-specific mTORC1 signaling mechanism that regulates T reg cell metabolism. |
