Macrophages regulate lung ILC2 activation via Pla2g5-dependent mechanisms.
Macrophages regulate lung ILC2 activation via Pla2g5-dependent mechanisms.
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DOI：
10.1038/mi.2017.99
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发表时间：
2018-05
影响因子：
8
通讯作者：
Balestrieri B
中科院分区：
文献类型：
--
作者：
Yamaguchi M;Samuchiwal SK;Quehenberger O;Boyce JA;Balestrieri B
V族磷脂酶A2（Pla 2g 5）是肺部炎症中巨噬细胞效应子功能所必需的脂质生成酶。然而，涉及的脂质介质及其细胞靶点尚未确定。缺乏Pla 2g 5的小鼠在反复吸入链格孢菌后显示出显著降低的肺ILC 2活化和嗜酸性粒细胞增多。虽然Pla 2g 5-null小鼠在一次链格孢属剂量后具有立即IL-33释放的Wt水平，但在重复链格孢属施用后，它们未能上调巨噬细胞中的IL-33。出乎意料的是，虽然过继转移骨髓来源的（BM）-巨噬细胞恢复了链格孢菌暴露的Pla 2g 5-null小鼠中的ILC 2活化和嗜酸性粒细胞增多，但外源性IL-33没有。相反，Pla 2g 5-null BM-巨噬细胞的转移减少了链格孢菌暴露的Wt小鼠中的炎症。游离脂肪酸（FFA）的质谱分析表明，在缺乏Pla 2g 5的肺和BM-巨噬细胞中，FFA（包括亚油酸（LA）和油酸（OA））显著减少。外源性给予野生型小鼠LA或LA+OA在体外和体内显著增强IL-33诱导的肺嗜酸性粒细胞增多和ILC 2扩增。相反，OA在Pla 2g 5缺失小鼠中增强IL-33诱导的炎症和ILC 2扩增，但LA在体内和体外均无活性。值得注意的是，与Wt ILC 2相比，Pla 2g 5-null ILC 2显示FFA-受体-1的表达显著降低。因此，巨噬细胞相关的Pla 2g 5通过调节IL-33诱导和FFA驱动的ILC 2活化而显著促进2型免疫。
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.
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DOI：
10.4049/jimmunol.1003020
发表时间：
2011-04-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kouzaki H;Iijima K;Kobayashi T;O'Grady SM;Kita H
通讯作者：
Kita H
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影响因子：
6.7
作者：
Gorski SA;Hahn YS;Braciale TJ
通讯作者：
Braciale TJ
DOI：
10.4049/jimmunol.1101632
发表时间：
2012-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Doherty TA;Khorram N;Sugimoto K;Sheppard D;Rosenthal P;Cho JY;Pham A;Miller M;Croft M;Broide DH
通讯作者：
Broide DH
影响因子：
32.4
作者：
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影响因子：
4.4
作者：
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通讯作者：
Leff, Alan R.