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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 d...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6122976/ https://www.ncbi.nlm.nih.gov/pubmed/30115741 http://dx.doi.org/10.1084/jem.20180397 |
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author | Yu, Xiaoyan Teng, Xiao-Lu Wang, Feixiang Zheng, Yuhan Qu, Guojun Zhou, Yan Hu, Zhilin Wu, Zhongqiu Chang, Yuzhou Chen, Lei Li, Hua-Bing Su, Bing Lu, Liming Liu, Zhiduo Sun, Shao-Cong Zou, Qiang |
author_facet | Yu, Xiaoyan Teng, Xiao-Lu Wang, Feixiang Zheng, Yuhan Qu, Guojun Zhou, Yan Hu, Zhilin Wu, Zhongqiu Chang, Yuzhou Chen, Lei Li, Hua-Bing Su, Bing Lu, Liming Liu, Zhiduo Sun, Shao-Cong Zou, Qiang |
author_sort | Yu, Xiaoyan |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6122976 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-61229762019-03-03 Metabolic control of regulatory T cell stability and function by TRAF3IP3 at the lysosome Yu, Xiaoyan Teng, Xiao-Lu Wang, Feixiang Zheng, Yuhan Qu, Guojun Zhou, Yan Hu, Zhilin Wu, Zhongqiu Chang, Yuzhou Chen, Lei Li, Hua-Bing Su, Bing Lu, Liming Liu, Zhiduo Sun, Shao-Cong Zou, Qiang J Exp Med Research Articles 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. Rockefeller University Press 2018-09-03 /pmc/articles/PMC6122976/ /pubmed/30115741 http://dx.doi.org/10.1084/jem.20180397 Text en © 2018 Yu et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Yu, Xiaoyan Teng, Xiao-Lu Wang, Feixiang Zheng, Yuhan Qu, Guojun Zhou, Yan Hu, Zhilin Wu, Zhongqiu Chang, Yuzhou Chen, Lei Li, Hua-Bing Su, Bing Lu, Liming Liu, Zhiduo Sun, Shao-Cong Zou, Qiang Metabolic control of regulatory T cell stability and function by TRAF3IP3 at the lysosome |
title | Metabolic control of regulatory T cell stability and function by TRAF3IP3 at the lysosome |
title_full | Metabolic control of regulatory T cell stability and function by TRAF3IP3 at the lysosome |
title_fullStr | Metabolic control of regulatory T cell stability and function by TRAF3IP3 at the lysosome |
title_full_unstemmed | Metabolic control of regulatory T cell stability and function by TRAF3IP3 at the lysosome |
title_short | Metabolic control of regulatory T cell stability and function by TRAF3IP3 at the lysosome |
title_sort | metabolic control of regulatory t cell stability and function by traf3ip3 at the lysosome |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6122976/ https://www.ncbi.nlm.nih.gov/pubmed/30115741 http://dx.doi.org/10.1084/jem.20180397 |
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