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Nat Commun. 2016 Nov 18;7:13559. doi: 10.1038/ncomms13559.

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

Li Y1, Lu Y2, Wang S1, Han Z3, Zhu F1, Ni Y4, Liang R1, Zhang Y5, Leng Q6, Wei G3, Shi G4, Zhu R7, Li D1, Wang H8, Zheng SG9,10, Xu H2, Tsun A1,11, Li B1,12,13.

Author information

1
Key Laboratory of Molecular Virology and Immunology, CAS Center for Excellence in Molecular Cell Science, Unit of Molecular Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China.
2
School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
3
Chinese Academy of Sciences-Max Planck Society (MPG) Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
4
Department of Pulmonary Medicine, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
5
Key Laboratory of Molecular Virology and Immunology, Unit of Hematopoietic Stem Cell and Transgenic Animal Model, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China.
6
Key Laboratory of Molecular Virology and Immunology, Unit of Immune Regulation, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China.
7
Flow Cytometry Core Facility, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China.
8
Key Laboratory of Molecular Virology and Immunology, Unit of the Regulation of Immune Cell Differentiation, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China.
9
Clinical Immunology Center, Third Affiliated Hospital at Sun Yat-Sen University, Guangzhou 510630, China.
10
Division of Rheumatology, Department of Medicine, Penn State University Hershey College of Medicine, Hershey, Pennsylvania 17033, USA.
11
Innovent Biologics (Suzhou) Co., Ltd, 168 Dongping Street, Suzhou Industrial Park, Suzhou, Jiangsu Province 215123, China.
12
Shanghai Institute of Immunology, Shanghai JiaoTong University School of Medicine, Shanghai 200025, China.
13
Department of Immunology and Microbiology, Shanghai JiaoTong University School of Medicine, Shanghai 200025, China.

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.

PMID:
27857073
PMCID:
PMC5120220
DOI:
10.1038/ncomms13559
[Indexed for MEDLINE]
Free PMC Article

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