Loss of PADI2 and PADI4 ameliorates sepsis-induced acute lung injury by suppressing NLRP3+ macrophages.

ABSTRACT: Sepsis-induced acute lung injury (ALI) is prevalent in patients with sepsis and has a high mortality rate. Peptidyl arginine deiminase 2 (PADI2) and PADI4 play crucial roles in mediating the host's immune response in sepsis, but their specific functions remain unclear. Our study shows that Padi2-/- Padi4-/- double KO (DKO) improved survival, reduced lung injury, and decreased bacterial load in Pseudomonas aeruginosa (PA) pneumonia-induced sepsis mice. Using single-cell RNA-Seq (scRNA-Seq), we found that the deletion of Padi2 and Padi4 reduced the Nlrp3+ proinflammatory macrophages and fostered Chil3+ myeloid cell differentiation into antiinflammatory macrophages. Additionally, we observed the regulatory role of the NLRP3/Ym1 axis upon DKO, confirmed by Chil3 knockdown and Nlrp3-KO experime

SUBMITTER: Yu X 

PROVIDER: S-EPMC11601939 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature