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ILC2s regulate adaptive Th2 cell functions via PD-L1 checkpoint control
Journal of Experimental Medicine ( IF 15.3 ) Pub Date : 2017-07-26 , DOI: 10.1084/jem.20170051
Christian Schwartz 1, 2 , Adnan R Khan 1, 2 , Achilleas Floudas 1, 2 , Sean P Saunders 1, 2 , Emily Hams 1, 2 , Hans-Reimer Rodewald 3 , Andrew N J McKenzie 4 , Padraic G Fallon 2, 5, 6
Affiliation  

Group 2 innate lymphoid cells (ILC2s) are important effector cells driving the initiation of type 2 immune responses leading to adaptive T helper 2 (Th2) immunity. Here we show that ILC2s dynamically express the checkpoint inhibitor molecule PD-L1 during type 2 pulmonary responses. Surprisingly, PD-L1:PD-1 interaction between ILC2s and CD4+ T cells did not inhibit the T cell response, but PD-L1–expressing ILC2s stimulated increased expression of GATA3 and production of IL-13 by Th2 cells both in vitro and in vivo. Conditional deletion of PD-L1 on ILC2s impaired early Th2 polarization and cytokine production, leading to delayed worm expulsion during infection with the gastrointestinal helminth Nippostrongylus brasiliensis. Our results identify a novel PD-L1–controlled mechanism for type 2 polarization, with ILC2s mediating an innate checkpoint to control adaptive T helper responses, which has important implications for the treatment of type 2 inflammation.



中文翻译:

ILC2s 通过 PD-L1 检查点控制调节自适应 Th2 细胞功能

第 2 组先天淋巴细胞 (ILC2) 是重要的效应细胞,可驱动引发 2 型免疫反应,从而产生适应性 T 辅助 2 (Th2) 免疫。在这里,我们显示 ILC2 在 2 型肺反应期间动态表达检查点抑制剂分子 PD-L1。令人惊讶的是,ILC2 和 CD4 + T 细胞之间的 PD-L1:PD-1 相互作用并未抑制 T 细胞反应,但表达 PD-L1 的 ILC2 在体外和体外刺激 Th2 细胞的 GATA3 表达和 IL-13 产生增加体内。ILC2 上 PD-L1 的条件性缺失损害了早期 Th2 极化和细胞因子的产生,导致在感染胃肠蠕虫Nippostrongylus brasiliensis期间蠕虫排出延迟. 我们的研究结果确定了一种新的 PD-L1 控制的 2 型极化机制,ILC2 介导先天检查点来控制适应性 T 辅助反应,这对 2 型炎症的治疗具有重要意义。

更新日期:2017-08-10
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