比利时列日大学Thomas Marichal和Fabrice Bureau等研究人员合作发现，局部引起的CXCR4高表达中性粒细胞通过释放中性粒细胞胞外陷阱触发环境引起的过敏性哮喘。该项研究成果在线发表于2019年10月7日的《自然—免疫学》。

通过使用单细胞RNA测序，研究人员表征了在接触屋尘螨之前，暴露于低促过敏剂量的脂多糖（LPS）或高剂量的LPS的小鼠肺中性粒细胞。与暴露于高剂量的LPS不同，暴露于低剂量的LPS指示招募的嗜中性粒细胞上调其趋化因子受体CXCR4的表达并释放嗜中性粒细胞胞外陷阱。低剂量LPS诱导的中性粒细胞和中性粒细胞胞外诱集剂可增强CD11b和Ly-6C双阳性树突状细胞对屋尘螨的捕获以及增加由屋尘螨引起的2型过敏性气道炎症。CXCR4高表达中性粒细胞产生的中性粒细胞外陷阱能够介导由流感病毒感染或暴露于臭氧引发的过敏性哮喘。这项研究表明，明显无关的环境危险因素可以影响被招募的肺中性粒细胞，从而促进过敏性哮喘的发作。

据悉，低暴露于微生物产物、呼吸道病毒感染和空气污染是过敏性哮喘的主要风险因素，但这些情况与宿主对2型过敏性疾病的易感性之间的机理联系仍不清楚。

附：英文原文

Title: Locally instructed CXCR4 hi neutrophils trigger environment-driven allergic asthma through the release of neutrophil extracellular traps

Author: Coraline Radermecker, Catherine Sabatel, Cline Vanwinge, Cecilia Ruscitti, Pauline Marchal, Fabienne Perin, Joey Schyns, Natacha Rocks, Marie Toussaint, Didier Cataldo, Sebastian L Johnston, Fabrice Bureau, Thomas Marichal

Issue&Volume: 2019-10-07

Abstract: Low exposure to microbial products, respiratory viral infections and air pollution are major risk factors for allergic asthma, yet the mechanistic links between such conditions and host susceptibility to type 2 allergic disorders remain unclear. Through the use of single-cell RNA sequencing, we characterized lung neutrophils in mice exposed to a pro-allergic low dose of lipopolysaccharide (LPS) or a protective high dose of LPS before exposure to house dust mites. Unlike exposure to a high dose of LPS, exposure to a low dose of LPS instructed recruited neutrophils to upregulate their expression of the chemokine receptor CXCR4 and to release neutrophil extracellular traps. Low-dose LPS–induced neutrophils and neutrophil extracellular traps potentiated the uptake of house dust mites by CD11b+Ly-6C+ dendritic cells and type 2 allergic airway inflammation in response to house dust mites. Neutrophil extracellular traps derived from CXCR4hi neutrophils were also needed to mediate allergic asthma triggered by infection with influenza virus or exposure to ozone. Our study indicates that apparently unrelated environmental risk factors can shape recruited lung neutrophils to promote the initiation of allergic asthma.

DOI: 10.1038/s41590-019-0496-9

Source: https://www.nature.com/articles/s41590-019-0496-9