Cutting Edge: IL-27 Attenuates Autoimmune Neuroinflammation via Regulatory T Cell/Lag3-Dependent but IL-10-Independent Mechanisms In Vivo
Cutting Edge: IL-27 Attenuates Autoimmune Neuroinflammation via Regulatory T Cell/Lag3-Dependent but IL-10-Independent Mechanisms In Vivo
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DOI：
10.4049/jimmunol.1800898
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发表时间：
2019-03-15
影响因子：
4.4
通讯作者：
Min, Booki
中科院分区：
文献类型：
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作者：
Kim, Dongkyun;Le, Hongnga T.;Min, Booki
IL-27在炎症中调节免疫反应。长期以来，IL-27功能的潜在机制一直被归因于它诱导活化的CD4T细胞产生IL-10的能力。在本研究中，我们报道了Foxp3(+)调节性T细胞(Tregs)是IL-27的主要靶细胞，在体内介导其免疫调节功能。系统递送的IL-27有效地防止了实验性自身免疫性脑脊髓炎的发展，这是中枢神经系统的一种自身免疫性炎症。然而，在Treg耗尽后，它未能做到这一点。IL-27在Tregs中的信号转导是必要的，因为转移缺乏IL-27Rα或由IL-27诱导的下游分子LAG3的Tregs不能保护小鼠免受实验性自身免疫性脑脊髓炎的影响。IL-27在体外能有效地诱导CD4T细胞表达IL-10，但我们没有发现支持IL-27诱导体内CD4T细胞表达IL-10的证据，我们的结果揭示了Tregs在IL-27介导的炎症控制中的不可替代的贡献。
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-27R alpha 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.