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 demonstrate that Th17 cell–associated experimental autoimmune encephalomyelitis was greatly exacerbated in Ctrp4^–/– mice compared with WT mice due to increased Th17 cell infiltration. The absence of Ctrp4 promoted the differentiation of naive CD4⁺ T cells into Th17 cells in vitro. Mechanistically, CTRP4 interfered with the interaction between IL-6 and the IL-6 receptor (IL-6R) by directly competing to bind with IL-6R, leading to suppression of IL-6–induced activation of the STAT3 pathway. Furthermore, the administration of recombinant CTRP4 protein ameliorated 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.

中文翻译：

---

CTRP4/白细胞介素 6 受体信号传导通过抑制 Th17 细胞分化改善自身免疫性脑脊髓炎

C1q/TNF 相关蛋白 4 (CTRP4) 通常被认为是在细胞外释放的，在能量代谢和预防脓毒症中发挥着关键作用。然而，其在自身免疫性疾病中的生理功能尚未得到彻底探索。在这项研究中，我们证明，与 WT 小鼠相比，由于 Th17 细胞浸润增加，Ctrp4 ^–/–小鼠的 Th17 细胞相关实验性自身免疫性脑脊髓炎大大加剧。 Ctrp4的缺失促进了初始CD4 ⁺ T细胞在体外分化为Th17细胞。从机制上讲，CTRP4 通过直接竞争与 IL-6R 的结合来干扰 IL-6 和 IL-6 受体 (IL-6R) 之间的相互作用，从而抑制 IL-6 诱导的 STAT3 通路的激活。此外，重组 CTRP4 蛋白的施用可改善疾病症状。总之，我们的结果表明 CTRP4 作为 IL-6 受体信号通路的内源性调节剂，可能是 Th17 驱动的自身免疫性疾病的潜在治疗干预措施。