Lipid metabolism-related genes are involved in the formation of macrophage extracellular traps in allergic airway inflammation.

Abstract

Recent studies have highlighted the critical role of lipid metabolism in macrophages concerning lung inflammation. However, it remains unclear whether lipid metabolism is involved in macrophage extracellular traps (METs). We analyzed the GSE40885 dataset from the GEO database using weighted correlation network analysis (WGCNA) and further selection using the least absolute shrinkage and selection operator (LASSO) regression. We identified ABCA1, SLC44A2, and C3 as key genes jointly involved in lipid metabolism and METs. Additionally, immune infiltration analysis was performed using the Xcell and CIBERSORT algorithms, while single-cell transcriptome analysis was utilized using data from the Tabula Muris database. The expression of key genes was validated in external datasets (GSE42606, GSE27066, GSE137268, and GSE256534). Notably, our results indicated that ABCA1 expression was elevated in patients experiencing acute asthma exacerbations, which aligned with its expression trend in lipopolysaccharide (LPS)-induced macrophages. However, ABCA1 expression was reduced in cases of chronic and severe asthma. Results from immunofluorescence (IF), SYTOX Green staining, and Western blot analyses suggested that ABCA1 may play a role in the formation of METs both in vivo and in vitro. In conclusion, this study indicates that ABCA1 may be involved in METs. ABCA1 may represent a promising therapeutic target for asthma.