Primary Data supporting "Neutrophil Heterogeneity is Modified during Acute Lung Inflammation in Apoa1-/- Mice."

Neutrophils play important roles in inflammatory airway diseases. Here, we assessed whether apolipoprotein A-I (apoA-I) modifies neutrophil heterogeneity as part of the mechanism by which it attenuates acute airway inflammation. Neutrophilic airway inflammation was induced by daily intranasal administration of LPS plus house dust mite (LPS+HDM) to <i>Apoa1</i>^-/- and <i>Apoa1</i>^+/+ mice for 3 days. Single cell RNA sequencing was performed on cells recovered from bronchoalveolar lavage fluid (BALF) on day 4. Unsupervised profiling identified 10 clusters of neutrophils in BALF from <i>Apoa1</i>^-/- and <i>Apoa1</i>^+/+ mice. LPS+HDM-challenged <i>Apoa1</i>^-/- mice had an increased proportion of the Neu4 neutrophil cluster that expressed <i>S100a8</i>, <i>S100a9</i>, and <i>Mmp8</i>, and had high maturation, aggregation, and TLR4 binding scores. There was also an increase in the Neu6 cluster of immature neutrophils, whereas neutrophil clusters expressing interferon-stimulated genes were decreased. An unsupervised trajectory analysis showed that Neu4 represented a distinct lineage in <i>Apoa1</i>^-/- mice. LPS+HDM-challenged <i>Apoa1</i>^-/- mice also had an increased proportion of recruited airspace macrophages, which was associated with a reciprocal reduction in resident airspace macrophages. Increased expression of a common set of pro-inflammatory genes, <i>S100a8</i>, <i>S100a9</i>, and <i>Lcn2</i>, was present in all neutrophils and airspace macrophages from LPS+HDM-challenged <i>Apoa1</i>^-/- mice. These findings show that <i>Apoa1</i>^-/- mice have increases in specific neutrophil and macrophage clusters in the lung during acute inflammation mediated by LPS+HDM, as well as enhanced expression of a common set of pro-inflammatory genes. This suggests that modifications in neutrophil and macrophage heterogeneity contribute to the mechanism by which apoA-I attenuates acute airway inflammation.