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Clinical Rheumatology

Erschienen in:

28.05.2020 | Original Article

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

verfasst von: Tingshuang Xu, Tianyi Yan, Ping Li

Erschienen in: Clinical Rheumatology | Ausgabe 12/2020

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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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Titel: Interleukin-29 regulates T follicular helper cells by repressing BCL6 in rheumatoid arthritis patients
verfasst von: Tingshuang Xu
Tianyi Yan
Ping Li
Publikationsdatum: 28.05.2020
Verlag: Springer International Publishing
Erschienen in: Clinical Rheumatology / Ausgabe 12/2020
Print ISSN: 0770-3198
Elektronische ISSN: 1434-9949
DOI: https://doi.org/10.1007/s10067-020-05151-y

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

Abstract

Introduction

Methods

Results

Conclusions

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Introduction

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