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

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.