Interleukin-29 regulates T follicular helper cells by repressing BCL6 in rheumatoid arthritis patients.

Tingshuang Xu, Tianyi Yan, Ping Li

Clinical rheumatology 2020 Dec

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We aimed to investigate whether Interleukin-29 (IL-29) directly affects T follicular helper (Tfh) cell frequency in rheumatoid arthritis (RA), which are both related to RA-specific antibody responses. Here, we explored the effect of IL-29 on Tfh cell production in RA patients using a combination of enzyme-linked immunosorbent assay (ELISA), flow cytometry (FCM), CD4+ T cell culture, western blotting, and reverse transcription-polymerase chain reaction (RT-PCR). We reported that serum IL-29 levels, peripheral blood CD4+CXCR5+ Tfh cell frequency, CD4+CXCR5+CD40L+ Tfh cell frequency, and IL-28 receptor (IL-28Rα) and IL-10 receptor (IL-10R2) levels in peripheral blood Tfh cells were higher in RA patients than in healthy controls (HCs). Serum IL-29 levels were positively correlated with peripheral blood CD4+CXCR5+CD40L+ Tfh cell frequency in RA patients, and both parameters also correlated with anti-cyclic citrullinated peptide (anti-CCP) antibodies. Furthermore, we showed that IL-29 may suppress Tfh cell differentiation in RA patients partly via decreased BCL6 level through reduced STAT3 activity. Taken together, our findings reveal the regulatory effect of IL-29 on Tfh cells, which participate in the pathogenesis of RA and provide new targets for its clinical treatment. Key Points • There is an increase in circulating Tfh cells and IL-29 levels in RA patients, which are correlated to anti-CCP antibodies levels and may be associated with RA pathogenesis. • We show for the first time that IL-29 may contribute to RA by inhibiting Tfh cell production, through decreasing the activity of STAT3 and downregulating the expression of BCL6. • The use of IL-29 biologics in patients with RA inhibits the production of Tfh cells, may prevent progression in patients with RA, and provides new targets for clinical treatment.

Citation

Tingshuang Xu, Tianyi Yan, Ping Li. Interleukin-29 regulates T follicular helper cells by repressing BCL6 in rheumatoid arthritis patients. Clinical rheumatology. 2020 Dec;39(12):3797-3804