Schistosoma japonicum Infection in Treg-Specific USP21 Knockout Mice
The E3 deubiquitinating enzyme ubiquitin-specific proteolytic enzyme 21 (USP21) plays vital roles in physiological activities and is required for Treg-cell-mediated immune tolerance. Using a murine model infected with Schistosoma japonicum, we observed that there were more cercariae developed into a...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2021-01-01
|
| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2021/6613162 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832564511764119552 |
|---|---|
| author | Youxiang Zhang De-Hui Xiong Yangyang Li Guina Xu Baoxin Zhang Yang Liu Shan Zhang Qing Huang Simin Chen Fansheng Zeng Jingyi Guo Bin Li Zhiqiang Qin Zuping Zhang |
| author_facet | Youxiang Zhang De-Hui Xiong Yangyang Li Guina Xu Baoxin Zhang Yang Liu Shan Zhang Qing Huang Simin Chen Fansheng Zeng Jingyi Guo Bin Li Zhiqiang Qin Zuping Zhang |
| author_sort | Youxiang Zhang |
| collection | DOAJ |
| description | The E3 deubiquitinating enzyme ubiquitin-specific proteolytic enzyme 21 (USP21) plays vital roles in physiological activities and is required for Treg-cell-mediated immune tolerance. Using a murine model infected with Schistosoma japonicum, we observed that there were more cercariae developed into adults and more eggs deposited in the livers of the USP21fl/flFOXP3Cre (KO) mice. However, immunohistochemistry showed that the degree of egg granuloma formation and liver fibrosis was reduced. In USP21fl/flFOXP3Cre mice, levels of IFN-gamma, IL-4, anti-soluble egg antigen (SEA) IgG and anti-soluble worm antigen preparation (SWAP) IgG increased in blood, as determined using ELISAs and multiplex fluorescent microsphere immunoassays, while the levels of IL-10, lL-17A, IL-23, IL-9, and anti-SEA IgM decreased. In addition, the levels of the USP21 protein and mRNA in the liver and spleen of KO mice decreased. We further observed increased Th1 responses amplified by Tregs (regulatory T cells) and compromised Th17 responses, which alleviated the liver immunopathology. We speculated that these changes were related to polarization of Th1-like Tregs. Our results revealed the roles of USP21 in Treg-cell-mediated regulation of immune interactions between Schistosoma and its host. USP21 may have potential for regulating hepatic fibrosis in patients with schistosomiasis. |
| format | Article |
| id | doaj-art-ec2e9387c1594235a59ce4b4af4766b4 |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-ec2e9387c1594235a59ce4b4af4766b42025-02-03T01:10:53ZengWileyJournal of Immunology Research2314-88612314-71562021-01-01202110.1155/2021/66131626613162Schistosoma japonicum Infection in Treg-Specific USP21 Knockout MiceYouxiang Zhang0De-Hui Xiong1Yangyang Li2Guina Xu3Baoxin Zhang4Yang Liu5Shan Zhang6Qing Huang7Simin Chen8Fansheng Zeng9Jingyi Guo10Bin Li11Zhiqiang Qin12Zuping Zhang13Department of Pathogen Biology, School of Basic Medical Science, Central South University, Changsha 410078, ChinaMolecular Biology Research Center, School of Life Science, Central South University, 110 Xiangya Road, Changsha, Hunan 410078, ChinaDepartment of Microbiology and Immunology, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaKey Laboratory of Control Technique for Schistosoma and Pathogen Infection for Dongting Lake Region, Yiyang Medical College, Yiyang 413002, ChinaDepartment of Epidemic Prevention, Armed Police Hospital of Hunan Province, Changsha, 410008 Hunan, ChinaSichuan Center for Disease Control and Prevention, Chengdu, 610041 Sichuan, ChinaDepartment of Pathogen Biology, School of Basic Medical Science, Central South University, Changsha 410078, ChinaDepartment of Pathogen Biology, School of Basic Medical Science, Central South University, Changsha 410078, ChinaDepartment of Pathogen Biology, School of Basic Medical Science, Central South University, Changsha 410078, ChinaKey Laboratory of Control Technique for Schistosoma and Pathogen Infection for Dongting Lake Region, Yiyang Medical College, Yiyang 413002, ChinaKey Laboratory of Parasite and Vector Biology, Ministry of Health; National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Chinese Center for Tropical Diseases Research, Shanghai 200025, ChinaDepartment of Microbiology and Immunology, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaKey Laboratory of Parasite and Vector Biology, Ministry of Health; National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Chinese Center for Tropical Diseases Research, Shanghai 200025, ChinaDepartment of Pathogen Biology, School of Basic Medical Science, Central South University, Changsha 410078, ChinaThe E3 deubiquitinating enzyme ubiquitin-specific proteolytic enzyme 21 (USP21) plays vital roles in physiological activities and is required for Treg-cell-mediated immune tolerance. Using a murine model infected with Schistosoma japonicum, we observed that there were more cercariae developed into adults and more eggs deposited in the livers of the USP21fl/flFOXP3Cre (KO) mice. However, immunohistochemistry showed that the degree of egg granuloma formation and liver fibrosis was reduced. In USP21fl/flFOXP3Cre mice, levels of IFN-gamma, IL-4, anti-soluble egg antigen (SEA) IgG and anti-soluble worm antigen preparation (SWAP) IgG increased in blood, as determined using ELISAs and multiplex fluorescent microsphere immunoassays, while the levels of IL-10, lL-17A, IL-23, IL-9, and anti-SEA IgM decreased. In addition, the levels of the USP21 protein and mRNA in the liver and spleen of KO mice decreased. We further observed increased Th1 responses amplified by Tregs (regulatory T cells) and compromised Th17 responses, which alleviated the liver immunopathology. We speculated that these changes were related to polarization of Th1-like Tregs. Our results revealed the roles of USP21 in Treg-cell-mediated regulation of immune interactions between Schistosoma and its host. USP21 may have potential for regulating hepatic fibrosis in patients with schistosomiasis.http://dx.doi.org/10.1155/2021/6613162 |
| spellingShingle | Youxiang Zhang De-Hui Xiong Yangyang Li Guina Xu Baoxin Zhang Yang Liu Shan Zhang Qing Huang Simin Chen Fansheng Zeng Jingyi Guo Bin Li Zhiqiang Qin Zuping Zhang Schistosoma japonicum Infection in Treg-Specific USP21 Knockout Mice Journal of Immunology Research |
| title | Schistosoma japonicum Infection in Treg-Specific USP21 Knockout Mice |
| title_full | Schistosoma japonicum Infection in Treg-Specific USP21 Knockout Mice |
| title_fullStr | Schistosoma japonicum Infection in Treg-Specific USP21 Knockout Mice |
| title_full_unstemmed | Schistosoma japonicum Infection in Treg-Specific USP21 Knockout Mice |
| title_short | Schistosoma japonicum Infection in Treg-Specific USP21 Knockout Mice |
| title_sort | schistosoma japonicum infection in treg specific usp21 knockout mice |
| url | http://dx.doi.org/10.1155/2021/6613162 |
| work_keys_str_mv | AT youxiangzhang schistosomajaponicuminfectionintregspecificusp21knockoutmice AT dehuixiong schistosomajaponicuminfectionintregspecificusp21knockoutmice AT yangyangli schistosomajaponicuminfectionintregspecificusp21knockoutmice AT guinaxu schistosomajaponicuminfectionintregspecificusp21knockoutmice AT baoxinzhang schistosomajaponicuminfectionintregspecificusp21knockoutmice AT yangliu schistosomajaponicuminfectionintregspecificusp21knockoutmice AT shanzhang schistosomajaponicuminfectionintregspecificusp21knockoutmice AT qinghuang schistosomajaponicuminfectionintregspecificusp21knockoutmice AT siminchen schistosomajaponicuminfectionintregspecificusp21knockoutmice AT fanshengzeng schistosomajaponicuminfectionintregspecificusp21knockoutmice AT jingyiguo schistosomajaponicuminfectionintregspecificusp21knockoutmice AT binli schistosomajaponicuminfectionintregspecificusp21knockoutmice AT zhiqiangqin schistosomajaponicuminfectionintregspecificusp21knockoutmice AT zupingzhang schistosomajaponicuminfectionintregspecificusp21knockoutmice |