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

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Abstract

Introduction

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.

Methods

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).

Results

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.

Conclusions

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.

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Acknowledgments

The authors acknowledge all members for their participation in this research.

Funding

This work was supported by the Department of Finance of Jilin Province (grant numbers bczby201706).

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Author notes

  1. Tingshuang Xu and Tianyi Yan contributed equally to this work.

Authors and Affiliations

  1. Department of Rheumatology and Immunology, China-Japan Union Hospital, Jilin University, No.126 Xiantai Street, Changchun, 130033, Jilin, China

    Tingshuang Xu, Tianyi Yan & Ping Li

  2. Jilin University First Hospital, Changchun, 130021, China

    Tingshuang Xu

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  1. Tingshuang Xu
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  2. Tianyi Yan
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Correspondence to Ping Li.

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Xu, T., Yan, T. & Li, P. Interleukin-29 regulates T follicular helper cells by repressing BCL6 in rheumatoid arthritis patients. Clin Rheumatol 39, 3797–3804 (2020). https://doi.org/10.1007/s10067-020-05151-y

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