USP21 prevents the generation of T-helper-1-like Treg cells

Yangyang Li; Yue Lu; Shuaiwei Wang; Zhijun Han; Fuxiang Zhu; Yingmeng Ni; Rui Liang; Yan Zhang; Qibin Leng; Gang Wei; Guochao Shi; Ruihong Zhu; Dan Li; Haikun Wang; Song Guo Zheng; Hongxi Xu; Andy Tsun; Bin Li

doi:10.1038/ncomms13559

USP21 prevents the generation of T-helper-1-like Treg cells

Yangyang Li, Yue Lu, Shuaiwei Wang, Zhijun Han, Fuxiang Zhu, Yingmeng Ni, Rui Liang, Yan Zhang, Qibin Leng, Gang Wei, Guochao Shi, Ruihong Zhu, Dan Li, Haikun Wang, Song Guo Zheng, Hongxi Xu, Andy Tsun, Bin Li

Department of Medicine

Research output: Contribution to journal › Article › peer-review

72 Scopus citations

Abstract

FOXP3 + Regulatory T (Treg) cells play a key role in the maintenance of immune homeostasis and tolerance. Disruption of Foxp3 expression results in the generation of instable Treg cells and acquisition of effector T-cell-like function. Here we report that the E3 deubiquitinase USP21 prevents the depletion of FOXP3 at the protein level and restricts the generation of T-helper-1-like Treg cells. Mice depleted of Usp21 specifically in Treg cells display immune disorders characterized by spontaneous T-cell activation and excessive T-helper type 1 (Th1) skewing of Treg cells into Th1-like Treg cells. USP21 stabilizes FOXP3 protein by mediating its deubiquitination and maintains the expression of Treg signature genes. Our results demonstrate how USP21 prevents FOXP3 protein depletion and controls Treg lineage stability in vivo.

Original language	English (US)
Article number	13559
Journal	Nature communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms13559
State	Published - Nov 18 2016

All Science Journal Classification (ASJC) codes

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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10.1038/ncomms13559

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title = "USP21 prevents the generation of T-helper-1-like Treg cells",

abstract = "FOXP3 + Regulatory T (Treg) cells play a key role in the maintenance of immune homeostasis and tolerance. Disruption of Foxp3 expression results in the generation of instable Treg cells and acquisition of effector T-cell-like function. Here we report that the E3 deubiquitinase USP21 prevents the depletion of FOXP3 at the protein level and restricts the generation of T-helper-1-like Treg cells. Mice depleted of Usp21 specifically in Treg cells display immune disorders characterized by spontaneous T-cell activation and excessive T-helper type 1 (Th1) skewing of Treg cells into Th1-like Treg cells. USP21 stabilizes FOXP3 protein by mediating its deubiquitination and maintains the expression of Treg signature genes. Our results demonstrate how USP21 prevents FOXP3 protein depletion and controls Treg lineage stability in vivo.",

author = "Yangyang Li and Yue Lu and Shuaiwei Wang and Zhijun Han and Fuxiang Zhu and Yingmeng Ni and Rui Liang and Yan Zhang and Qibin Leng and Gang Wei and Guochao Shi and Ruihong Zhu and Dan Li and Haikun Wang and Zheng, {Song Guo} and Hongxi Xu and Andy Tsun and Bin Li",

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doi = "10.1038/ncomms13559",

language = "English (US)",

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AU - Li, Yangyang

AU - Lu, Yue

AU - Wang, Shuaiwei

AU - Han, Zhijun

AU - Zhu, Fuxiang

AU - Ni, Yingmeng

AU - Liang, Rui

AU - Zhang, Yan

AU - Leng, Qibin

AU - Wei, Gang

AU - Shi, Guochao

AU - Zhu, Ruihong

AU - Li, Dan

AU - Wang, Haikun

AU - Zheng, Song Guo

AU - Xu, Hongxi

AU - Tsun, Andy

AU - Li, Bin

PY - 2016/11/18

Y1 - 2016/11/18

N2 - FOXP3 + Regulatory T (Treg) cells play a key role in the maintenance of immune homeostasis and tolerance. Disruption of Foxp3 expression results in the generation of instable Treg cells and acquisition of effector T-cell-like function. Here we report that the E3 deubiquitinase USP21 prevents the depletion of FOXP3 at the protein level and restricts the generation of T-helper-1-like Treg cells. Mice depleted of Usp21 specifically in Treg cells display immune disorders characterized by spontaneous T-cell activation and excessive T-helper type 1 (Th1) skewing of Treg cells into Th1-like Treg cells. USP21 stabilizes FOXP3 protein by mediating its deubiquitination and maintains the expression of Treg signature genes. Our results demonstrate how USP21 prevents FOXP3 protein depletion and controls Treg lineage stability in vivo.

AB - FOXP3 + Regulatory T (Treg) cells play a key role in the maintenance of immune homeostasis and tolerance. Disruption of Foxp3 expression results in the generation of instable Treg cells and acquisition of effector T-cell-like function. Here we report that the E3 deubiquitinase USP21 prevents the depletion of FOXP3 at the protein level and restricts the generation of T-helper-1-like Treg cells. Mice depleted of Usp21 specifically in Treg cells display immune disorders characterized by spontaneous T-cell activation and excessive T-helper type 1 (Th1) skewing of Treg cells into Th1-like Treg cells. USP21 stabilizes FOXP3 protein by mediating its deubiquitination and maintains the expression of Treg signature genes. Our results demonstrate how USP21 prevents FOXP3 protein depletion and controls Treg lineage stability in vivo.

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JO - Nature communications

JF - Nature communications

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USP21 prevents the generation of T-helper-1-like Treg cells

Abstract

All Science Journal Classification (ASJC) codes

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