Ubiquitin-specific peptidase 18 regulates the differentiation and function of Treg cells
Ubiquitin-specific peptidase 18 (USP18) plays an important role in the development of CD11b+ dendritic cells (DCs) and Th17 cells, however, its role in the differentiation of other T cell subsets, especially in regulatory T (Treg) cells, is unknown. In our study, we used Usp18 KO mice to study the l...
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KeAi Communications Co., Ltd.
2021-05-01
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| Series: | Genes and Diseases |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352304220300465 |
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| author | Lu Yang Yukai Jing Danqing Kang Panpan Jiang Na Li Xinrong Zhou Yan Chen Lisa S. Westerberg Chaohong Liu |
| author_facet | Lu Yang Yukai Jing Danqing Kang Panpan Jiang Na Li Xinrong Zhou Yan Chen Lisa S. Westerberg Chaohong Liu |
| author_sort | Lu Yang |
| collection | DOAJ |
| description | Ubiquitin-specific peptidase 18 (USP18) plays an important role in the development of CD11b+ dendritic cells (DCs) and Th17 cells, however, its role in the differentiation of other T cell subsets, especially in regulatory T (Treg) cells, is unknown. In our study, we used Usp18 KO mice to study the loss of USP18 on the impact of Treg cell differentiation and function. We found that USP18 deficiency upregulates the differentiation of Treg cells, which may lead to disrupted homeostasis of peripheral T cells, and downregulates INF-γ, IL-2, IL-17A producing CD4+ T cells and INF-γ producing CD8+ T cells. Mechanistically, we also found that the upregulation of Tregs is due to elevated expression of CD25 in Usp18 KO mice. Finally, we found that the suppressive function of Usp18 KO Tregs is downregulated. Altogether, our study was the first to identify the role of USP18 in Tregs differentiation and its suppressive function, which may provide a new reference for the treatment of Treg function in many autoimmune diseases, and USP18 can be used as a new therapeutic target for precise medical treatment. |
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| id | doaj.art-ffa6ec6b041648b79e5b56b47d81f9be |
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| issn | 2352-3042 |
| language | English |
| last_indexed | 2025-03-22T04:32:52Z |
| publishDate | 2021-05-01 |
| publisher | KeAi Communications Co., Ltd. |
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| series | Genes and Diseases |
| spelling | doaj.art-ffa6ec6b041648b79e5b56b47d81f9be2024-04-28T03:00:14ZengKeAi Communications Co., Ltd.Genes and Diseases2352-30422021-05-0183344352Ubiquitin-specific peptidase 18 regulates the differentiation and function of Treg cellsLu Yang0Yukai Jing1Danqing Kang2Panpan Jiang3Na Li4Xinrong Zhou5Yan Chen6Lisa S. Westerberg7Chaohong Liu8Department of Pathogen Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430030, PR ChinaDepartment of Pathogen Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430030, PR ChinaDepartment of Pathogen Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430030, PR ChinaDepartment of Pathogen Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430030, PR ChinaDepartment of Immunology, School of Medicine, Yangtze University, Jingzhou, Hubei Province, 434023, PR ChinaDepartment of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430030, PR ChinaThe Second Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, Zunyi, GuiZhou Province, 563000, PR ChinaDepartment of Microbiology Tumor and Cell Biology, Karolinska Institutet, Stockholm, 17177, SwedenDepartment of Pathogen Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430030, PR China; Corresponding author. Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan 430030, China. Fax: +86 27 8365 0550.Ubiquitin-specific peptidase 18 (USP18) plays an important role in the development of CD11b+ dendritic cells (DCs) and Th17 cells, however, its role in the differentiation of other T cell subsets, especially in regulatory T (Treg) cells, is unknown. In our study, we used Usp18 KO mice to study the loss of USP18 on the impact of Treg cell differentiation and function. We found that USP18 deficiency upregulates the differentiation of Treg cells, which may lead to disrupted homeostasis of peripheral T cells, and downregulates INF-γ, IL-2, IL-17A producing CD4+ T cells and INF-γ producing CD8+ T cells. Mechanistically, we also found that the upregulation of Tregs is due to elevated expression of CD25 in Usp18 KO mice. Finally, we found that the suppressive function of Usp18 KO Tregs is downregulated. Altogether, our study was the first to identify the role of USP18 in Tregs differentiation and its suppressive function, which may provide a new reference for the treatment of Treg function in many autoimmune diseases, and USP18 can be used as a new therapeutic target for precise medical treatment.http://www.sciencedirect.com/science/article/pii/S2352304220300465CD25Foxp3ICOSRegulator T cellUSP18 |
| spellingShingle | Lu Yang Yukai Jing Danqing Kang Panpan Jiang Na Li Xinrong Zhou Yan Chen Lisa S. Westerberg Chaohong Liu Ubiquitin-specific peptidase 18 regulates the differentiation and function of Treg cells Genes and Diseases CD25 Foxp3 ICOS Regulator T cell USP18 |
| title | Ubiquitin-specific peptidase 18 regulates the differentiation and function of Treg cells |
| title_full | Ubiquitin-specific peptidase 18 regulates the differentiation and function of Treg cells |
| title_fullStr | Ubiquitin-specific peptidase 18 regulates the differentiation and function of Treg cells |
| title_full_unstemmed | Ubiquitin-specific peptidase 18 regulates the differentiation and function of Treg cells |
| title_short | Ubiquitin-specific peptidase 18 regulates the differentiation and function of Treg cells |
| title_sort | ubiquitin specific peptidase 18 regulates the differentiation and function of treg cells |
| topic | CD25 Foxp3 ICOS Regulator T cell USP18 |
| url | http://www.sciencedirect.com/science/article/pii/S2352304220300465 |
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