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

作者：Xiaoyan Yu, Xiao-Lu Teng, Feixiang Wang, Yuhan Zheng, Guojun Qu, Yan Zhou, Zhilin Hu, Zhongqiu Wu, Yuzhou Chang, Lei Chen, Huabing Li, Bing Su, Liming Lu, Zhiduo Liu, Shao‐Cong Sun, Qiang Zou · 发表于：The Journal of Experimental Medicine · 年份：2018 · DOI：10.1084/jem.20180397 · 被引用次数：102 · 研究领域：Immune Cell Function and Interaction、T-cell and B-cell Immunology、Calcium signaling and nucleotide metabolism

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.