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Fibroblast-like synoviocytes (FLS) are critical in promoting inflammation and cartilage destruction in rheumatoid arthritis (RA), and the interaction between FLS and T cells is considered to facilitate FLS activation and T cell recruitment. However, it remains unknown whether RA-FLS co-cultured with activated peripheral blood mononuclear cells (PBMC) has immunoregulatory effects on peripheral Tfh. In the present study, we co-cultured RA-FLS with or without anti-CD3\/CD28-stimulated PBMC. The results showed that RA-FLS co-cultured with stimulated PBMC could increase the numbers of CD4+CXCR5+ICOS+ T cells of RA PBMC possibly via the production of interleukin (IL)-6, a critical cytokine involved in the differentiation of Tfh cells. We also observed increased reactive oxygen species (ROS) levels in the co-culture system of RA-FLS and PBMC. The percentage of CD4+CXCR5+ICOS+ T cells was decreased when ROS production was inhibited by N-acetyl-L-cysteine (NAC), a specific inhibitor which can decrease ROS production. In addition, we showed that the higher levels of tumour necrosis factor (TNF)-\u03b1 and IL-1\u03b2 in the co-culture system and the blocking of TNF receptor 2 (TNF-R2) and IL-1\u03b2 receptor (IL-1\u03b2R) both decreased the numbers of CD4+CXCR5+ICOS+ T cells. Our study reveals a novel mechanistic insight into how the interaction of RA-FLS and PBMC participates in the RA pathogenesis, and also provides support for the biologicals application for RA.<\/jats:p>","DOI":"10.1111\/cei.13025","type":"journal-article","created":{"date-parts":[[2017,8,19]],"date-time":"2017-08-19T04:52:38Z","timestamp":1503118358000},"page":"384-393","source":"Crossref","is-referenced-by-count":37,"title":["Rheumatoid arthritis fibroblast-like synoviocytes co-cultured with PBMC increased peripheral CD4+CXCR5+ICOS+ T cell numbers"],"prefix":"10.1093","volume":"190","author":[{"given":"Y","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Immunology, College of Basic Medical Science, Dalian Medical University, 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