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CTRP4/Interleukin-6 receptor signaling ameliorates autoimmune encephalomyelitis by suppressing Th17 cell differentiation

Cao, L;Deng, J;Chen, W;He, M;Zhao, N;Huang, H;Ling, L;Li, Q;Zhu, X;Wang, L;

C1q/TNF related protein 4 (CTRP4) is generally thought to be released extracellularly and plays a critical role in energy metabolism and protecting against sepsis. However, its physiological functions in autoimmune diseases have not been thoroughly explored. In this study, we demonstrated that Th17 cell-associated experimental autoimmune encephalomyelitis was greatly exacerbated in Ctrp4-/- mice compared to WT mice due to increased Th17 cell infiltration. The absence of Ctrp4 promoted the differentiation of naïve CD4+ T cells into Th17 cells in vitro. Mechanistically, CTRP4 interferes with the interaction between IL-6 and IL-6R by directly competing to bind with IL-6R leading to suppression of IL-6-induced activation of STAT3 pathway. Furthermore, the administration of recombinant CTRP4 protein ameliorated the disease symptoms. In conclusion, our results indicate that CTRP4, as an endogenous regulator of the IL-6 receptor signaling pathway, may be a potential therapeutic intervention for Th17 driven-autoimmune diseases.