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FRI0050 CYR61 induces IL-6 production by fibroblast-like synoviocytes promoting TH17 differentiation in rheumatoid arthritis
  1. N.L. Li1,
  2. J. Lin1,
  3. Z. Zhou2,
  4. R. Huo1,
  5. L. Xiao3,
  6. G. Ouyang3,
  7. N. Li2
  1. 1Shanghai Institute of Immunology, Shanghai Jiaotong University
  2. 2Shanghai Institute of Immunology
  3. 3Guanghua Rheumatology Hospital, Shanghai, China

Abstract

Background Cyr61/CCN1 is a product of an immediate early gene which functions in mediating cell adhesion and inducing cell migration. We previously showed that increased production of Cyr61 by fibroblast-like synoviocytes (FLS) in RA promotes FLS proliferation and participates in RA pathogenesis with IL-17 dependent pathway. However, whether Cyr61 in turn regulates Th17 cell differentiation and further enhances inflammation of RA remained unknown.

Objectives To explored the potential role of Cyr61 as a pro-inflammatory factor to promote Th17 differentiation in RA pathogenesis.

Methods Th17 differentiation was studied in a co-culture system of CD4+ T and FLS cells. Collagen-induced arthritis (CIA) mice were used as the RA animal model to test the therapeutic effect of anti-Cyr61 antibody as well as its effect on IL-6 production by FLS and Th17 differentiation in vivo. Expression of cytokines was measured by ELISA, real-time PCR and flow cytometry, other factors by real-time PCR, western blotting or confocal microscopy.

Results Cyr61 stimulated IL-6 production by FLS, via the Cyr61/αvβ5/Akt/NF-kB signaling pathway. Increased IL-6 in turn promoted Th17 differentiation. Blocking Cyr61 action with a monoclonal antibody (093G9) reduced IL-6 production by FLS, attenuated Th17 response, and ameliorated disease progression in CIA mice.

Conclusions Cyr61 plays a critical role in stimulating IL-6 expression by FLS in RA and contributes to Th17 cell differentiation, and thus is likely a key molecule involved in the inflammation process of RA. Targeting Cyr61 may be a novel therapeutic strategy for RA.

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Disclosure of Interest None Declared

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