Laboratory of Mucosal Immunology in Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
Department of Life Sciences and Division of Integrative Biosciences & Biotechnology, Pohang University of Science & Technology (POSTECH), Pohang, Republic of Korea.
J Allergy Clin Immunol. 2022 Apr;149(4):1253-1269.e8. doi: 10.1016/j.jaci.2021.09.031. Epub 2021 Oct 20.
Diesel exhaust particles (DEPs) are the main component of traffic-related air pollution and have been implicated in the pathogenesis and exacerbation of asthma. However, the mechanism by which DEP exposure aggravates asthma symptoms remains unclear.
This study aimed to identify a key cellular player of air pollutant-induced asthma exacerbation and development.
We examined the distribution of innate immune cells in the murine models of asthma induced by house dust mite and DEP. Changes in immune cell profiles caused by DEP exposure were confirmed by flow cytometry and RNA-Seq analysis. The roles of sialic acid-binding, Ig-like lectin F (SiglecF)-positive neutrophils were further evaluated by adoptive transfer experiment and in vitro functional studies.
DEP exposure induced a unique population of lung granulocytes that coexpressed Ly6G and SiglecF. These cells differed phenotypically, morphologically, functionally, and transcriptionally from other SiglecF-expressing cells in the lungs. Our findings with murine models suggest that intratracheal challenge with DEPs induces the local release of adenosine triphosphate, which is a damage-associated molecular pattern signal. Adenosine triphosphate promotes the expression of SiglecF on neutrophils, and these SiglecF neutrophils worsen type 2 and 3 airway inflammation by producing high levels of cysteinyl leukotrienes and neutrophil extracellular traps. We also found Siglec8- (which corresponds to murine SiglecF) expressing neutrophils, and we found it in patients with asthma-chronic obstructive pulmonary disease overlap.
The SiglecF neutrophil is a novel and critical player in airway inflammation and targeting this population could reverse or ameliorate asthma.
柴油废气颗粒（DEP）是交通相关空气污染的主要成分，已被牵连到哮喘的发病和恶化中。然而，DEP 暴露加重哮喘症状的机制仍不清楚。
本研究旨在确定一种导致空气污染物诱发的哮喘恶化和发展的关键细胞参与者。
我们检查了屋尘螨和 DEP 诱导的哮喘小鼠模型中固有免疫细胞的分布。通过流式细胞术和 RNA-Seq 分析证实了 DEP 暴露引起的免疫细胞谱变化。通过过继转移实验和体外功能研究进一步评估了唾液酸结合免疫球蛋白样凝集素 F（SiglecF）阳性中性粒细胞的作用。
DEP 暴露诱导了一种独特的肺部粒细胞群体，该群体共同表达 Ly6G 和 SiglecF。这些细胞在表型、形态、功能和转录上与肺部其他表达 SiglecF 的细胞不同。我们用小鼠模型的研究结果表明，DEP 气管内挑战诱导局部释放三磷酸腺苷，这是一种损伤相关分子模式信号。三磷酸腺苷促进中性粒细胞上 SiglecF 的表达，这些 SiglecF 中性粒细胞通过产生高水平的半胱氨酰白三烯和中性粒细胞细胞外陷阱，加重 2 型和 3 型气道炎症。我们还发现 Siglec8（对应于小鼠 SiglecF）表达的中性粒细胞，并在哮喘-慢性阻塞性肺疾病重叠患者中发现了它。
SiglecF 中性粒细胞是气道炎症的一个新的和关键的参与者，针对这个群体可能会逆转或改善哮喘。
