Secreted PLA2 group X orchestrates innate and adaptive immune responses to inhaled allergen.

Secreted PLA2 group X orchestrates innate and adaptive immune responses to inhaled allergen.
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分泌的 PLA2 X 组协调对吸入过敏原的先天和适应性免疫反应。

DOI:
10.1172/jci.insight.94929
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发表时间:
2017
期刊:
影响因子:
8
通讯作者:
Hallstrand,TealS
Hallstrand,TealS
中科院分区:
医学1区
文献类型:
--
作者:
Nolin,JamesD;Lai,Ying;Ogden,HerbertLuke;Manicone,AnneM;Murphy,RyanC;An,Dowon;Frevert,CharlesW;Ghomashchi,Farideh;Naika,GajendraS;Gelb,MichaelH;Gauvreau,GailM;Piliponsky,AdrianM;Altemeier,WilliamA;Hallstrand,TealS

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磷脂酶A2 (PLA2)酶调节促成过敏性气道炎症的类二十烷和溶血磷脂的形成。最近发现,在哮喘患者的气道中,分泌的PLA2组X (sPLA2-X)增加,并在气道上皮细胞和巨噬细胞中高度表达。在目前的研究中,我们发现人类和小鼠的过敏原暴露增加了sPLA2-X,并且Pla2g10的全局缺失导致气道高反应性(AHR),嗜酸性粒细胞和T细胞向气道运输,气道闭塞,抗原刺激的白细胞产生2型细胞因子和抗原特异性免疫球蛋白的显着减少。此外,我们发现Pla2g10 - / -小鼠BALF中IL-33水平降低,肺中2型先天淋巴细胞(ILC2s)减少,肥大细胞中IL-33诱导的IL-13表达减少,新招募的巨噬细胞数量和这些巨噬细胞在肺中的M2极化均显著减少。这些结果表明sPLA2-X在对蛋白水解过敏原的先天和适应性免疫反应中起中心调节作用。
Phospholipase A2 (PLA2) enzymes regulate the formation of eicosanoids and lysophospholipids that contribute to allergic airway inflammation. Secreted PLA2 group X (sPLA2-X) was recently found to be increased in the airways of asthmatics and is highly expressed in airway epithelial cells and macrophages. In the current study, we show that allergen exposure increases sPLA2-X in humans and in mice, and that global deletion of Pla2g10 results in a marked reduction in airway hyperresponsiveness (AHR), eosinophil and T cell trafficking to the airways, airway occlusion, generation of type-2 cytokines by antigen-stimulated leukocytes, and antigen-specific immunoglobulins. Further, we found that Pla2g10–/– mice had reduced IL-33 levels in BALF, fewer type-2 innate lymphoid cells (ILC2s) in the lung, less IL-33–induced IL-13 expression in mast cells, and a marked reduction in both the number of newly recruited macrophages and the M2 polarization of these macrophages in the lung. These results indicate that sPLA2-X serves as a central regulator of both innate and adaptive immune response to proteolytic allergen.
内源性分泌型磷脂酶 A2 X 组调节人嗜酸性粒细胞的半胱氨酰白三烯合成。
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