A unique population of neutrophils generated by air pollutant-induced lung damage exacerbates airway inflammation.

Background 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. Objective This study aims to identify a key cellular player of air pollutant-induced asthma exacerbation and development. Methods We examined the distribution of innate immune cells in the murine models of asthma induced by house dust mite (HDM) and DEP. Changes in immune cell profiles caused by DEP exposure were confirmed by flow cytometry, RNA seq analysis. The roles of Sialic acid-binding, Ig-like lectin F (SiglecF)+ neutrophils were further evaluated by adoptive transfer experiment and in vitro functional studies. Results We show here that DEP exposure induces a unique population of lung granulocytes that co-express Ly-6G and sialic acid-binding, Ig-like lectin (Siglec)-F. These cells differ phenotypically, morphologically, functionally, and transcriptionally from other SiglecF-expressing cells in the lungs. Our findings with murine models suggest that intratracheal challenge with DEP induces the local release of adenosine 5'-​triphosphate (ATP), which is a damage-associated molecular pattern (DAMP) signal. ATP 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 in the patients with asthma-COPD overlap (ACO). Conclusion SiglecF+ neutrophil is a novel and critical player in airway inflammation and targeting the populations could reverse or ameliorate asthma.