2. Academic Validation
  3. Metabolic control of regulatory T cell stability and function by TRAF3IP3 at the lysosome

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

  • J Exp Med. 2018 Sep 3;215(9):2463-2476. doi: 10.1084/jem.20180397.
Xiaoyan Yu 1,  Xiao-Lu Teng 1,  Feixiang Wang 1,  Yuhan Zheng 1,  Guojun Qu 1,  Yan Zhou 1,  Zhilin Hu 1,  Zhongqiu Wu 1,  Yuzhou Chang 1,  Lei Chen 1,  Hua-Bing Li 1,  Bing Su 1,  Liming Lu 2,  Zhiduo Liu 3,  Shao-Cong Sun 4,  Qiang Zou 5
Affiliations

Affiliations

  • 1 Shanghai Institute of Immunology, Department of Immunology and Microbiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 2 Shanghai Institute of Immunology, Department of Immunology and Microbiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China lulunew2002@aliyun.com.
  • 3 Shanghai Institute of Immunology, Department of Immunology and Microbiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China zhiduo.liu@shsmu.edu.cn.
  • 4 Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX ssun@mdanderson.org.
  • 5 Shanghai Institute of Immunology, Department of Immunology and Microbiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China Qzou1984@sjtu.edu.cn.
PMID: 30115741 DOI: 10.1084/jem.20180397
Abstract

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.

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