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ZFP91 is required for the maintenance of regulatory T cell homeostasis and function

Autophagy programs the metabolic and functional fitness of regulatory T (T reg) cells to establish immune tolerance, yet the mechanisms governing autophagy initiation in T reg cells remain unclear. Here, we show that the E3 ubiquitin ligase ZFP91 facilitates autophagy activation to sustain T reg cel...

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Autores principales: Wang, Aiting, Ding, Lei, Wu, Zhongqiu, Ding, Rui, Teng, Xiao-Lu, Wang, Feixiang, Hu, Zhilin, Chen, Lei, Yu, Xiaoyan, Zou, Qiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769166/
https://www.ncbi.nlm.nih.gov/pubmed/33355624
http://dx.doi.org/10.1084/jem.20201217
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author Wang, Aiting
Ding, Lei
Wu, Zhongqiu
Ding, Rui
Teng, Xiao-Lu
Wang, Feixiang
Hu, Zhilin
Chen, Lei
Yu, Xiaoyan
Zou, Qiang
author_facet Wang, Aiting
Ding, Lei
Wu, Zhongqiu
Ding, Rui
Teng, Xiao-Lu
Wang, Feixiang
Hu, Zhilin
Chen, Lei
Yu, Xiaoyan
Zou, Qiang
author_sort Wang, Aiting
collection PubMed
description Autophagy programs the metabolic and functional fitness of regulatory T (T reg) cells to establish immune tolerance, yet the mechanisms governing autophagy initiation in T reg cells remain unclear. Here, we show that the E3 ubiquitin ligase ZFP91 facilitates autophagy activation to sustain T reg cell metabolic programming and functional integrity. T reg cell–specific deletion of Zfp91 caused T reg cell dysfunction and exacerbated colonic inflammation and inflammation-driven colon carcinogenesis. TCR-triggered autophagy induction largely relied on T reg cell–derived ZFP91 to restrict hyperglycolysis, which is required for the maintenance of T reg cell homeostasis. Mechanistically, ZFP91 rapidly translocated from the nucleus to the cytoplasm in response to TCR stimulation and then mediated BECN1 ubiquitination to promote BECN1–PIK3C3 complex formation. Therefore, our results highlight a ZFP91-dependent mechanism promoting TCR-initiated autophagosome maturation to maintain T reg cell homeostasis and function.
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spelling pubmed-77691662021-08-01 ZFP91 is required for the maintenance of regulatory T cell homeostasis and function Wang, Aiting Ding, Lei Wu, Zhongqiu Ding, Rui Teng, Xiao-Lu Wang, Feixiang Hu, Zhilin Chen, Lei Yu, Xiaoyan Zou, Qiang J Exp Med Article Autophagy programs the metabolic and functional fitness of regulatory T (T reg) cells to establish immune tolerance, yet the mechanisms governing autophagy initiation in T reg cells remain unclear. Here, we show that the E3 ubiquitin ligase ZFP91 facilitates autophagy activation to sustain T reg cell metabolic programming and functional integrity. T reg cell–specific deletion of Zfp91 caused T reg cell dysfunction and exacerbated colonic inflammation and inflammation-driven colon carcinogenesis. TCR-triggered autophagy induction largely relied on T reg cell–derived ZFP91 to restrict hyperglycolysis, which is required for the maintenance of T reg cell homeostasis. Mechanistically, ZFP91 rapidly translocated from the nucleus to the cytoplasm in response to TCR stimulation and then mediated BECN1 ubiquitination to promote BECN1–PIK3C3 complex formation. Therefore, our results highlight a ZFP91-dependent mechanism promoting TCR-initiated autophagosome maturation to maintain T reg cell homeostasis and function. Rockefeller University Press 2020-12-23 /pmc/articles/PMC7769166/ /pubmed/33355624 http://dx.doi.org/10.1084/jem.20201217 Text en © 2020 Wang 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 Article
Wang, Aiting
Ding, Lei
Wu, Zhongqiu
Ding, Rui
Teng, Xiao-Lu
Wang, Feixiang
Hu, Zhilin
Chen, Lei
Yu, Xiaoyan
Zou, Qiang
ZFP91 is required for the maintenance of regulatory T cell homeostasis and function
title ZFP91 is required for the maintenance of regulatory T cell homeostasis and function
title_full ZFP91 is required for the maintenance of regulatory T cell homeostasis and function
title_fullStr ZFP91 is required for the maintenance of regulatory T cell homeostasis and function
title_full_unstemmed ZFP91 is required for the maintenance of regulatory T cell homeostasis and function
title_short ZFP91 is required for the maintenance of regulatory T cell homeostasis and function
title_sort zfp91 is required for the maintenance of regulatory t cell homeostasis and function
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769166/
https://www.ncbi.nlm.nih.gov/pubmed/33355624
http://dx.doi.org/10.1084/jem.20201217
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