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 [email protected].
  • 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 [email protected].
  • 4 Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX [email protected].
  • 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 [email protected].
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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