1] Klinikum rechts der Isar, Department of Neurology, Technische Universität München, Ismaninger Straße 22, 81675 Munich, Germany [2].
Klinikum rechts der Isar, Department of Neurology, Technische Universität München, Ismaninger Straße 22, 81675 Munich, Germany.
Nat Commun. 2014 May 6;5:3770. doi: 10.1038/ncomms4770.
Central nervous system (CNS) autoimmunity is regulated by the balance of pro-inflammatory cytokines and IL-10. Here we identify the transcriptional regulator Blimp1 as crucial to induce IL-10 in inflammatory T helper cells. Pre-committed Th17 cells respond to IL-27 and IL-12 by upregulating Blimp1 and adopt a Tr-1-like phenotype characterized by IL-10 and IFN-γ production. Accordingly, Blimp1-deficient effector T cells fail to produce IL-10, and deficiency in Tr-1 cell function leads to uncontrolled Th17 cell-driven CNS pathology without the need to stabilize the Th17 phenotype with IL-23. IL-23 counteracts IL-27 and IL-12-mediated effects on Tr-1-development reinforcing the pro-inflammatory phenotype of Th17 cells. Thus, the balance of IL-23 vs IL-12/IL-27 signals into CD4(+) effector T cells determines whether tissue inflammation is perpetuated or resolves.
中枢神经系统（CNS）自身免疫由促炎细胞因子和 IL-10 的平衡调节。在这里，我们确定转录调节因子 Blimp1 对于在炎症性辅助性 T 细胞中诱导 IL-10 至关重要。预先定型的 Th17 细胞通过上调 Blimp1 对 IL-27 和 IL-12 作出反应，并采用以产生 IL-10 和 IFN-γ为特征的 Tr-1 样表型。相应地，缺乏 Blimp1 的效应 T 细胞不能产生 IL-10，而 Tr-1 细胞功能的缺乏导致不受控制的 Th17 细胞驱动的中枢神经系统病理，而无需用 IL-23 稳定 Th17 表型。IL-23 拮抗 IL-27 和 IL-12 对 Tr-1 发育的影响，加强 Th17 细胞的促炎表型。因此，IL-23 与 IL-12/IL-27 信号进入 CD4(+)效应 T 细胞的平衡决定了组织炎症是持续存在还是得到解决。
Zotero 插件