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.
authors.affiliation: 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.
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Li
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Lu
authors.affiliation: 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.
authors.forename: Shuaiwei
authors.initials: S
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Han
authors.affiliation: 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.
authors.forename: Fuxiang
authors.initials: F
authors.lastname: Zhu
authors.affiliation: Department of Pulmonary Medicine, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
authors.forename: Yingmeng
authors.initials: Y
authors.lastname: Ni
authors.affiliation: 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.
authors.forename: Rui
authors.initials: R
authors.lastname: Liang
authors.affiliation: 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.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Qibin
authors.identifier: 0000-0002-4768-1312
authors.initials: Q
authors.lastname: Leng
authors.affiliation: 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.
authors.forename: Gang
authors.initials: G
authors.lastname: Wei
authors.affiliation: Department of Pulmonary Medicine, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
authors.forename: Guochao
authors.initials: G
authors.lastname: Shi
authors.affiliation: Flow Cytometry Core Facility, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China.
authors.forename: Ruihong
authors.initials: R
authors.lastname: Zhu
authors.affiliation: 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.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Haikun
authors.initials: H
authors.lastname: Wang
authors.affiliation: Clinical Immunology Center, Third Affiliated Hospital at Sun Yat-Sen University, Guangzhou 510630, China.|Division of Rheumatology, Department of Medicine, Penn State University Hershey College of Medicine, Hershey, Pennsylvania 17033, USA.
authors.forename: Song Guo
authors.initials: SG
authors.lastname: Zheng
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Hongxi
authors.initials: H
authors.lastname: Xu
authors.affiliation: 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.|Innovent Biologics (Suzhou) Co., Ltd, 168 Dongping Street, Suzhou Industrial Park, Suzhou, Jiangsu Province 215123, China.
authors.forename: Andy
authors.initials: A
authors.lastname: Tsun
authors.affiliation: 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.|Shanghai Institute of Immunology, Shanghai JiaoTong University School of Medicine, Shanghai 200025, China.|Department of Immunology and Microbiology, Shanghai JiaoTong University School of Medicine, Shanghai 200025, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
mesh_terms: D000818:Animals; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D018345:Mice, Knockout; D050378:T-Lymphocytes, Regulatory / Q000145:classification* / Q000502:physiology; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000378:metabolism*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C408875:USP21 protein, human; C584021:Usp16 protein, mouse; D043222:Ubiquitin Thiolesterase