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- Title
Hypoxia-inducible factor-1α regulates the interleukin-6 production by B cells in rheumatoid arthritis.
- Authors
Chaofan Fan; Jia Li; Yixuan Li; Yuyang Jin; Jiaqi Feng; Ruru Guo; Xinyu Meng; Dongcheng Gong; Qian Chen; Fang Du; Chunyan Zhang; Liangjing Lu; Jun Deng; Xiao-Xiang Chen
- Abstract
Objectives. Rheumatoid arthritis (RA) is a disease characterised by bone destruction and systemic inflammation, and interleukin-6 (IL-6) is a therapeutic target for treating it. The study aimed at investigating the sources of IL-6 and the influence of hypoxia-inducible factor-1α (HIF-1α) on IL-6 production by B cells in RA patients. Methods. The phenotype of IL-6-producing cells in the peripheral blood of RA patients was analysed using flow cytometry. Bioinformatics, real-time polymerase chain reaction, Western blot and immunofluorescence staining were used to determine the IL-6 production and HIF-1α levels in B cells. A dualluciferase reporter assay and chromatin immunoprecipitation were used to investigate the regulatory role of HIF-1α on IL-6 production in human and mouse B cells. Results. Our findings revealed that B cells are major sources of IL-6 in the peripheral blood of RA patients, with the proportion of IL-6-producing B cells significantly correlated with RA disease activity. The CD27-IgD+ naïve B cell subset was identified as the typical IL-6-producing subset in RA patients. Both HIF-1α and IL-6 were co-expressed by B cells in the peripheral blood and synovium of RA patients, and HIF-1α was found to directly bind to the IL6 promoter and enhance its transcription. Conclusion. This study highlights the role of B cells in producing IL-6 and the regulation of this production by HIF-1α in patients with RA. Targeting HIF-1α might provide a new therapeutic strategy for treating RA.
- Subjects
B cells; RHEUMATOID arthritis; INTERLEUKIN-6; BLOOD cells; POLYMERASE chain reaction
- Publication
Clinical & Translational Immunology, 2023, Vol 12, Issue 5, p1
- ISSN
2050-0068
- Publication type
Article
- DOI
10.1002/cti2.1447