Distinctive CD39⁺CD9⁺ lung interstitial macrophages suppress IL-23/Th17-mediated neutrophilic asthma by inhibiting NETosis.

ABSTRACT: The IL-23-Th17 axis is responsible for neutrophilic inflammation in various inflammatory diseases. Here, we discover a potential pathway to inhibit neutrophilic asthma. In our neutrophil-dominant asthma (NDA) model, single-cell RNA-seq analysis identifies a subpopulation of CD39⁺CD9⁺ interstitial macrophages (IMs) suppressed by IL-23 in NDA conditions but increased by an IL-23 inhibitor αIL-23p19. Adoptively transferred CD39⁺CD9⁺ IMs suppress neutrophil extracellular trap formation (NETosis), a representative phenotype of NDA, and also Th17 cell activation and neutrophilic inflammation. CD39⁺CD9⁺ IMs first attach to neutrophils in a CD9-dependent manner, and then remove ATP near neutrophils that contribute to NETosis in a CD

SUBMITTER: Han S 

PROVIDER: S-EPMC11452667 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature