Caveolin-1/PPARα axis suppresses T follicular helper cell response in primary Sjögren disease
Summary: T follicular helper (Tfh) cells play a central role in humoral autoimmunity, including primary Sjögren disease (SjD). However, targeting Tfh cells in clinical management is challenging. Previous studies suggest that inducible T cell co-stimulator (ICOS) directs Tfh cell motility in engaging...
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| Language: | English |
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Elsevier
2025-08-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725009271 |
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| author | Sulan Yu Meiling Wu Weizhen Zeng Weiwei Fu Yacun Chen Jing Xie Philip Hei Li Yun Feng Jiangang Shen Xiang Lin |
| author_facet | Sulan Yu Meiling Wu Weizhen Zeng Weiwei Fu Yacun Chen Jing Xie Philip Hei Li Yun Feng Jiangang Shen Xiang Lin |
| author_sort | Sulan Yu |
| collection | DOAJ |
| description | Summary: T follicular helper (Tfh) cells play a central role in humoral autoimmunity, including primary Sjögren disease (SjD). However, targeting Tfh cells in clinical management is challenging. Previous studies suggest that inducible T cell co-stimulator (ICOS) directs Tfh cell motility in engaging bystander B cells and promoting plasma cell differentiation. Herein, we took advantage of the mouse model of experimental Sjögren syndrome (ESS) and identified an unappreciated role of caveolin-1 (Cav-1) in suppressing ICOS expression in Tfh cells and SjD pathogenesis. Peroxisome proliferator-activated receptor alpha (PPARα), a transcription factor downstream of Cav-1, rapidly repressed Icos transcription upon Tfh polarization, independent of lipid metabolism. Both Cav-1 and PPARα were decreased in CD4+ T cells from patients with SjD and ESS mice. Notably, the pharmaceutical agonist of PPARα suppressed human and murine Tfh cell responses both in vitro and in vivo and effectively ameliorated the disease pathology of ESS mice with chronic inflammation. |
| format | Article |
| id | doaj-art-c2d35854d84a48658730fdbe929170b9 |
| institution | Kabale University |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-c2d35854d84a48658730fdbe929170b92025-08-20T03:36:35ZengElsevierCell Reports2211-12472025-08-0144811615610.1016/j.celrep.2025.116156Caveolin-1/PPARα axis suppresses T follicular helper cell response in primary Sjögren diseaseSulan Yu0Meiling Wu1Weizhen Zeng2Weiwei Fu3Yacun Chen4Jing Xie5Philip Hei Li6Yun Feng7Jiangang Shen8Xiang Lin9School of Chinese Medicine, The University of Hong Kong, Hong Kong SAR, ChinaSchool of Chinese Medicine, The University of Hong Kong, Hong Kong SAR, China; State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong SAR, ChinaDepartment of Ophthalmology, Peking University Third Hospital, Beijing, ChinaDepartment of Gastroenterology, Peking University Third Hospital, Beijing, ChinaSchool of Chinese Medicine, The University of Hong Kong, Hong Kong SAR, ChinaSchool of Chinese Medicine, The University of Hong Kong, Hong Kong SAR, ChinaDivision of Rheumatology and Clinical Immunology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR, ChinaDepartment of Ophthalmology, Peking University First Hospital, Beijing, China; Corresponding authorSchool of Chinese Medicine, The University of Hong Kong, Hong Kong SAR, China; State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong SAR, China; Corresponding authorSchool of Chinese Medicine, The University of Hong Kong, Hong Kong SAR, China; State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong SAR, China; Corresponding authorSummary: T follicular helper (Tfh) cells play a central role in humoral autoimmunity, including primary Sjögren disease (SjD). However, targeting Tfh cells in clinical management is challenging. Previous studies suggest that inducible T cell co-stimulator (ICOS) directs Tfh cell motility in engaging bystander B cells and promoting plasma cell differentiation. Herein, we took advantage of the mouse model of experimental Sjögren syndrome (ESS) and identified an unappreciated role of caveolin-1 (Cav-1) in suppressing ICOS expression in Tfh cells and SjD pathogenesis. Peroxisome proliferator-activated receptor alpha (PPARα), a transcription factor downstream of Cav-1, rapidly repressed Icos transcription upon Tfh polarization, independent of lipid metabolism. Both Cav-1 and PPARα were decreased in CD4+ T cells from patients with SjD and ESS mice. Notably, the pharmaceutical agonist of PPARα suppressed human and murine Tfh cell responses both in vitro and in vivo and effectively ameliorated the disease pathology of ESS mice with chronic inflammation.http://www.sciencedirect.com/science/article/pii/S2211124725009271CP: Immunology |
| spellingShingle | Sulan Yu Meiling Wu Weizhen Zeng Weiwei Fu Yacun Chen Jing Xie Philip Hei Li Yun Feng Jiangang Shen Xiang Lin Caveolin-1/PPARα axis suppresses T follicular helper cell response in primary Sjögren disease Cell Reports CP: Immunology |
| title | Caveolin-1/PPARα axis suppresses T follicular helper cell response in primary Sjögren disease |
| title_full | Caveolin-1/PPARα axis suppresses T follicular helper cell response in primary Sjögren disease |
| title_fullStr | Caveolin-1/PPARα axis suppresses T follicular helper cell response in primary Sjögren disease |
| title_full_unstemmed | Caveolin-1/PPARα axis suppresses T follicular helper cell response in primary Sjögren disease |
| title_short | Caveolin-1/PPARα axis suppresses T follicular helper cell response in primary Sjögren disease |
| title_sort | caveolin 1 pparα axis suppresses t follicular helper cell response in primary sjogren disease |
| topic | CP: Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725009271 |
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