Background We previously showed that adiponectin (AD) acts to promote Th17 cell differentiation, suggesting that AD plays an important role in mediating joint inflammation and damage in collagen-induced arthritis (CIA).
Objectives The aim of this study was to investigate whether STAT3 expression is regulated by AD, and if so, whether knockdown AdipoR1 could inhibit STAT3 and Th17 expression and prevent disease progression in CIA.
Methods Expression of Th17, AD and STAT3 in joint tissue of CIA was detected by real-time PCR and flow cytometry. STAT3 promoter activity was analyzed using a Dual-Luciferase Reporter Assay. The effect of AD on STAT3 expression in vitro and vivo was assessed using histological analysis, real-time PCR and flow cytometry.
Results Expression of STAT3 was up-regulated and positively correlated with highly expressed AD in joint tissue of CIA. Moreover, AD treatment markedly enhanced STAT3 expression both in vitro and vivo. Moreover, we found that the anti-Th17 differentiation effect of STAT3 inhibitor can be stimulated by addition of exogenous AD partly. Mechanistically, we showed AD activated STAT3 transcription by binding to the promoter region of the STAT3 gene. Further, using the CIA model, we showed that treatment with the AdipoR1 RNA interference led to reduction of STAT3 levels, decrease of Th17 response, and attenuation of inflammation and disease progression in vivo.
Conclusions Our results not only reveal a new role of AD in promoting Th17 development via upregulation of STAT3 expression. Our study also suggests that the pro-Th17 cell differentiation effect of AD is mediated through AdipoR1.
Disclosure of Interest None declared
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