Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195.
Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195
J Immunol. 2019 Mar 15;202(6):1680-1685. doi: 10.4049/jimmunol.1800898. Epub 2019 Jan 30.
IL-27 regulates immune responses in inflammation. The underlying mechanism of IL-27 functions has long been attributed to its ability to induce IL-10 production in activated CD4 T cells. In this study, we report that Foxp3 regulatory T cells (Tregs) are the main target cells of IL-27, mediating its immunoregulatory functions in vivo. Systemically delivered IL-27 efficiently prevents the development of experimental autoimmune encephalomyelitis, an autoimmune inflammation in the CNS. However, it failed to do so upon Treg depletion. IL-27 signaling in Tregs was necessary, as transferring Tregs deficient in IL-27Rα or Lag3, a downstream molecule induced by IL-27, was unable to protect mice from experimental autoimmune encephalomyelitis. IL-27 efficiently induced IL-10 expression in CD4 T cells in vitro; however, we found no evidence supporting IL-27-induced IL-10 induction in CD4 T cells in vivo. Taken together, our results uncover an irreplaceable contribution of Tregs during IL-27-mediated control of inflammation.
IL-27 调节炎症中的免疫反应。IL-27 功能的潜在机制长期以来归因于其诱导活化的 CD4 T 细胞产生 IL-10 的能力。在这项研究中，我们报告 Foxp3 调节性 T 细胞（Tregs）是 IL-27 的主要靶细胞，介导其在体内的免疫调节功能。全身性给予 IL-27 可有效预防实验性自身免疫性脑脊髓炎的发生，这是中枢神经系统的自身免疫性炎症。然而，在 Treg 耗竭时，它未能做到这一点。Treg 中的 IL-27 信号是必需的，因为缺乏 IL-27Rα 或 Lag3（IL-27 诱导的下游分子）的 Treg 无法保护小鼠免受实验性自身免疫性脑脊髓炎的侵害。IL-27 在体外可有效诱导 CD4 T 细胞表达 IL-10；然而，我们没有发现证据支持体内 IL-27 诱导 CD4 T 细胞中 IL-10 的诱导。总之，我们的结果揭示了 Tregs 在 IL-27 介导的炎症控制中不可或缺的贡献。
