Treg/Th17失衡是介导非嗜酸性粒细胞性哮喘（NEA）的关键。近年来发现 IL-6促进可塑性的Treg向Th17转化。IL-6通过膜受体（mIL-6R）经典途径和可溶受体（sIL-6R）反向途径发挥作用。有研究显示ATP诱导Treg产生蛋白酶ADAM17，水解mIL-6R成为sIL-6R，形成IL-6/sIL-6R（Hyper-IL-6）反向信号。我们前期研究发现，NEA小鼠给予ATP受体拮抗剂或IL-6反向抑制剂均能减轻Th17极化，而 Hyper-IL-6体外可促使Treg转化为Th17。据此假设，NEA小鼠气道ATP通过诱导Treg胞膜ADAM17，水解mIL-6R，产生Hyper-IL-6，促进Treg转化为Th17，导致Treg/Th17失衡。故本课题拟体内外实验，探讨ATP/ADAM17/Hyper-IL-6轴介导Treg转化为Th17的分子机制，为防治NEA提供新策略。

The imbalance of Th17/Treg polarization is a key pathogenesis to NEA. Recently, it has been found that IL-6 promotes the transformation of plasticitic Treg into Th17. IL-6 plays its role through the classical pathway by membrane receptor (mIL-6R) and the trans-signalling pathway by soluble receptor (sIL-6R). Studies have shown that ATP induces Treg to produce protease ADAM17, then hydrolyze mIL-6R into sIL-6R, and form trans-signalling of IL-6/sIL-6R (Hyper-IL-6).Our previous studies have shown that antagonist of ATP receptor or inhibitor of IL-6 trans-signalling can alleviate Th17 polarization in NEA mice, while Hyper-IL-6 can promote Treg to transform into Th17 in vitro. According to this,we put forward the hypothesis that ATP in airway of NEA mice induces ADAM17 on membrane of Treg, then hydrolyzes mIL-6R, and forms Hyper-IL-6, finally promotes Treg transform into Th17, and results into the imbalance of Treg/Th17. Therefore, we intend to explore the molecular mechanism of transformation of Treg into mediated by Th17 ATP/ADAM17/Hyper-IL-6 axis in vivo and in vitro, and provide a new strategy for the prevention and treatment of NEA.