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Iguratimod suppresses Tfh cell differentiation in primary Sjögren’s syndrome patients through inhibiting Akt/mTOR/STAT3 signaling
- Source :
- Arthritis Research & Therapy, Vol 25, Iss 1, Pp 1-11 (2023)
- Publication Year :
- 2023
- Publisher :
- BMC, 2023.
-
Abstract
- Abstract Background Iguratimod (IGU) reduces hypergammaglobulinemia and disease activity in pSS (primary Sjögren’s syndrome) patients. However, the therapeutical mechanism of IGU for pSS remains largely unknown. This study aimed to investigate the regulation of Tfh cell differentiation by IGU in pSS patients. Methods We prospectively enrolled 13 pSS patients treated with IGU for 3 months and examined circulating T cell and B cell subsets by flow cytometry. We measured Tfh cell differentiation treated by IGU in pSS patients and healthy controls. Transcriptome analysis combined with molecular docking were employed to identify potential therapeutical targets of IGU, which were verified by Western blot and Tfh cell differentiation. Results Tfh, plasmablast, and plasma cells were suppressed by IGU treatment at 1 and 3 months. Tfh cell differentiation and function were significant inhibited by IGU in pSS patients and healthy controls in vitro. Pyruvate dehydrogenase kinase 1 (PDK1) was identified as a target of IGU during Tfh cell differentiation, and the downstream Akt phosphorylation was attenuated by IGU. Moreover, the activity of mTORC1 and phosphorylation of STAT3 were suppressed by IGU, with downregulation of BCL6 and upregulation of PRDM1. Finally, Akt activator restored IGU-suppressed Tfh cell differentiation. Conclusions IGU suppresses Tfh cell differentiation in pSS patients through interacting with PDK1 and suppressing Akt-mTOR-STAT3 signaling.
Details
- Language :
- English
- ISSN :
- 14786362
- Volume :
- 25
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Arthritis Research & Therapy
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.20ce3f72143d4090bebdbd7ba94eab55
- Document Type :
- article
- Full Text :
- https://doi.org/10.1186/s13075-023-03109-4