Summary:
Basophils play critical roles in the development of mouse delayed-onset skin allergic inflammation (IgE-CAI model). Importantly, they also contribute to the resolution of allergic inflammation by promoting the generation of pro-resolving macrophages. However, it remains unclear how pro-resolving macrophages suppress excess inflammation. To address this, we conducted single-cell RNA-seq (scRNA-seq) analysis of the IgE-CAI skin lesion at days 3 and 5 post-challenge of allergens. scRNA-seq analysis identified two distinct classical monocyte-derived macrophage (CMDM) populations, namely early and late CMDMs, in IgE-CAI skin lesion. The former population was preferentially observed at the peak of inflammation (day 3), whereas the latter one at the termination phase of inflammation (day 5). Gene ontology analysis revealed that genes associated with phagocytosis were enriched in late CMDMs. In particular, late CMDMs displayed upregulated expression of Gas6 and Mertk, key genes for phagocytic clearance of apoptotic cells. Taken together, scRNA-seq identified CMDMs that display high capacity of dead cell clearance and contribute to the resolution of IgE-CAI.
