Metabolic control of regulatory T cell stability and function by TRAF3IP3 at the lysosome

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.

Source: The Journal of Experimental Medicine - September 3, 2018 Category: Internal Medicine Authors: Yu, X., Teng, X.-L., Wang, F., Zheng, Y., Qu, G., Zhou, Y., Hu, Z., Wu, Z., Chang, Y., Chen, L., Li, H.-B., Su, B., Lu, L., Liu, Z., Sun, S.-C., Zou, Q. Tags: Tumor Immunology, Tolerance Articles Source Type: research