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Single cell RNA sequencing identifies unique inflammatory airspace macrophage subsets

Mould, KJ;Jackson, ND;Henson, PM;Seibold, MA;Janssen, WJ;

Macrophages are well-recognized for their dual roles in orchestrating inflammatory responses and regulating tissue repair. In almost all acutely inflamed tissues, two main subclasses of macrophages co-exist. These include embryonically-derived resident tissue macrophages and bone marrow-derived recruited macrophages. While it is clear that macrophage subsets categorized in this fashion display distinct transcriptional and functional profiles, whether all cells within these categories and in the same inflammatory microenvironment share similar functions or whether further specialization exists has not been determined. To investigate inflammatory macrophage heterogeneity on a more granular level, we induced acute lung inflammation in mice and performed single cell RNA sequencing of macrophages isolated from the airspaces during health, peak inflammation, and resolution of inflammation. In doing so, we confirm that cell origin is the major determinant of AM programing and describe two previously uncharacterized, transcriptionally distinct subdivisions of AMs based on proliferative capacity and inflammatory programing.