USP25 attenuates anti-GBM nephritis in mice by negative feedback regulation of Th17 cell differentiation
Purpose This study aimed to elucidate the role of USP25 in a mouse model of anti-glomerular basement membrane glomerulonephritis (anti-GBM GN).Methods USP25-deficient anti-GBM GN mice were generated, and their nephritis progression was monitored. Naïve CD4+ T cells were isolated from spleen lymphocy...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Renal Failure |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/0886022X.2024.2338932 |
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| author | Ranran Xu Fei Huang Qingquan Liu Yongman Lv Liu Hu Qian Zhang |
| author_facet | Ranran Xu Fei Huang Qingquan Liu Yongman Lv Liu Hu Qian Zhang |
| author_sort | Ranran Xu |
| collection | DOAJ |
| description | Purpose This study aimed to elucidate the role of USP25 in a mouse model of anti-glomerular basement membrane glomerulonephritis (anti-GBM GN).Methods USP25-deficient anti-GBM GN mice were generated, and their nephritis progression was monitored. Naïve CD4+ T cells were isolated from spleen lymphocytes and stimulated to differentiate into Th1, Th2, and Th17 cells. This approach was used to investigate the impact of USP25 on CD4+ T lymphocyte differentiation in vitro. Furthermore, changes in USP25 expression were monitored during Th17 differentiation, both in vivo and in vitro.Results USP25−/− mice with anti-GBM GN exhibited accelerated renal function deterioration, increased infiltration of Th1 and Th17 cells, and elevated RORγt transcription. In vitro experiments demonstrated that USP25−/− CD4+ T lymphocytes had a higher proportion for Th17 cell differentiation and exhibited higher RORγt levels upon stimulation. Wild-type mice with anti-GBM GN showed higher USP25 levels compared to healthy mice, and a positive correlation was observed between USP25 levels and Th17 cell counts. Similar trends were observed in vitro.Conclusion USP25 plays a crucial role in mitigating renal histopathological and functional damage during anti-GBM GN in mice. This protective effect is primarily attributed to USP25’s ability to inhibit the differentiation of naïve CD4+ T cells into Th17 cells. The underlying mechanism may involve the downregulation of RORγt. Additionally, during increased inflammatory responses or Th17 cell differentiation, USP25 expression is activated, forming a negative feedback regulatory loop that attenuates immune activation. |
| format | Article |
| id | doaj-art-d243aebfe1b64dc499fbb1d793f60017 |
| institution | Kabale University |
| issn | 0886-022X 1525-6049 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Renal Failure |
| spelling | doaj-art-d243aebfe1b64dc499fbb1d793f600172025-01-23T04:17:49ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492024-12-0146110.1080/0886022X.2024.2338932USP25 attenuates anti-GBM nephritis in mice by negative feedback regulation of Th17 cell differentiationRanran Xu0Fei Huang1Qingquan Liu2Yongman Lv3Liu Hu4Qian Zhang5Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. ChinaDepartment of General Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. ChinaDepartment of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. ChinaDepartment of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. ChinaHealth Management Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. ChinaDepartment of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. ChinaPurpose This study aimed to elucidate the role of USP25 in a mouse model of anti-glomerular basement membrane glomerulonephritis (anti-GBM GN).Methods USP25-deficient anti-GBM GN mice were generated, and their nephritis progression was monitored. Naïve CD4+ T cells were isolated from spleen lymphocytes and stimulated to differentiate into Th1, Th2, and Th17 cells. This approach was used to investigate the impact of USP25 on CD4+ T lymphocyte differentiation in vitro. Furthermore, changes in USP25 expression were monitored during Th17 differentiation, both in vivo and in vitro.Results USP25−/− mice with anti-GBM GN exhibited accelerated renal function deterioration, increased infiltration of Th1 and Th17 cells, and elevated RORγt transcription. In vitro experiments demonstrated that USP25−/− CD4+ T lymphocytes had a higher proportion for Th17 cell differentiation and exhibited higher RORγt levels upon stimulation. Wild-type mice with anti-GBM GN showed higher USP25 levels compared to healthy mice, and a positive correlation was observed between USP25 levels and Th17 cell counts. Similar trends were observed in vitro.Conclusion USP25 plays a crucial role in mitigating renal histopathological and functional damage during anti-GBM GN in mice. This protective effect is primarily attributed to USP25’s ability to inhibit the differentiation of naïve CD4+ T cells into Th17 cells. The underlying mechanism may involve the downregulation of RORγt. Additionally, during increased inflammatory responses or Th17 cell differentiation, USP25 expression is activated, forming a negative feedback regulatory loop that attenuates immune activation.https://www.tandfonline.com/doi/10.1080/0886022X.2024.2338932USP25anti-GBM GNTh17 cellsRORγt |
| spellingShingle | Ranran Xu Fei Huang Qingquan Liu Yongman Lv Liu Hu Qian Zhang USP25 attenuates anti-GBM nephritis in mice by negative feedback regulation of Th17 cell differentiation Renal Failure USP25 anti-GBM GN Th17 cells RORγt |
| title | USP25 attenuates anti-GBM nephritis in mice by negative feedback regulation of Th17 cell differentiation |
| title_full | USP25 attenuates anti-GBM nephritis in mice by negative feedback regulation of Th17 cell differentiation |
| title_fullStr | USP25 attenuates anti-GBM nephritis in mice by negative feedback regulation of Th17 cell differentiation |
| title_full_unstemmed | USP25 attenuates anti-GBM nephritis in mice by negative feedback regulation of Th17 cell differentiation |
| title_short | USP25 attenuates anti-GBM nephritis in mice by negative feedback regulation of Th17 cell differentiation |
| title_sort | usp25 attenuates anti gbm nephritis in mice by negative feedback regulation of th17 cell differentiation |
| topic | USP25 anti-GBM GN Th17 cells RORγt |
| url | https://www.tandfonline.com/doi/10.1080/0886022X.2024.2338932 |
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