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Macrophages regulate lung ILC2 activation via Pla2g5-dependent mechanisms.
Mucosal Immunology ( IF 8 ) Pub Date : 2017-12-20 , DOI: 10.1038/mi.2017.99
M Yamaguchi 1 , S K Samuchiwal 1 , O Quehenberger 2 , J A Boyce 1 , B Balestrieri 1
Affiliation  

Group V phospholipase A2 (Pla2g5) is a lipid-generating enzyme necessary for macrophage effector functions in pulmonary inflammation. However, the lipid mediators involved and their cellular targets have not been identified. Mice lacking Pla2g5 showed markedly reduced lung ILC2 activation and eosinophilia following repetitive Alternaria Alternata inhalation. While Pla2g5-null mice had Wt levels of immediate IL-33 release after one Alternaria dose, they failed to upregulate IL-33 in macrophages following repeated Alternaria administration. Unexpectedly, while adoptive transfer of bone marrow-derived (BM)-macrophages restored ILC2 activation and eosinophilia in Alternaria-exposed Pla2g5-null mice, exogenous IL-33 did not. Conversely, transfers of Pla2g5-null BM-macrophages reduced inflammation in Alternaria-exposed Wt mice. Mass spectrometry analysis of free fatty acids (FFAs) demonstrated significantly reduced FFAs (including linoleic acid (LA) and oleic acid (OA)) in lung and BM-macrophages lacking Pla2g5. Exogenous administration of LA or LA+OA to Wt mice sharply potentiated IL-33-induced lung eosinophilia and ILC2 expansion in vitro and in vivo. In contrast, OA potentiated IL-33-induced inflammation and ILC2 expansion in Pla2g5-null mice, but LA was inactive both in vivo and in vitro. Notably, Pla2g5-null ILC2s showed significantly reduced expression of the FFA-receptor-1 compared to Wt ILC2s. Thus, macrophage-associated Pla2g5 contributes significantly to type-2 immunity through regulation of IL-33 induction and FFA-driven ILC2 activation.

中文翻译:

巨噬细胞通过 Pla2g5 依赖机制调节肺 ILC2 激活。

V 组磷脂酶 A2 (Pla2g5) 是肺部炎症中巨噬细胞效应器功能所必需的脂质生成酶。然而,尚未确定所涉及的脂质介质及其细胞靶标。缺乏 Pla2g5 的小鼠在重复吸入链格孢后表现出显着降低的肺 ILC2 活化和嗜酸性粒细胞增多。虽然 Pla2g5 缺失小鼠在一次链格孢属给药后具有 Wt 水平的立即释放 IL-33,但在重复施用链格孢属后它们未能上调巨噬细胞中的 IL-33。出乎意料的是,虽然骨髓来源 (BM) 巨噬细胞的过继转移恢复了链格孢菌暴露的 Pla2g5 缺失小鼠中的 ILC2 活化和嗜酸性粒细胞增多,但外源性 IL-33 却没有。相反,Pla2g5-null BM-巨噬细胞的转移减少了暴露于链格孢菌的 Wt 小鼠的炎症。游离脂肪酸 (FFA) 的质谱分析表明,在缺乏 Pla2g5 的肺和 BM-巨噬细胞中,游离脂肪酸 (包括亚油酸 (LA) 和油酸 (OA)) 显着减少。向 Wt 小鼠外源性施用 LA 或 LA+OA 会在体外和体内显着增强 IL-33 诱导的肺嗜酸性粒细胞增多和 ILC2 扩增。相反,OA 在 Pla2g5 缺失小鼠中增强了 IL-33 诱导的炎症和 ILC2 扩增,但 LA 在体内和体外均无活性。值得注意的是,与 Wt ILC2 相比,Pla2g5-null ILC2 显示出 FFA-receptor-1 的表达显着降低。因此,巨噬细胞相关的 Pla2g5 通过调节 IL-33 诱导和 FFA 驱动的 ILC2 激活显着促进 2 型免疫。
更新日期:2017-12-20
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