Novel Sca-1⁺ macrophages modulate the pathogenic progress of endotoxemia

Macrophages are important innate immune cells that play crucial roles in inflammatory responses. Accumulating evidence has demonstrated macrophage heterogeneity based on biomarkers, functions, and localization. Here, we report a novel stem cell antigen-1 (Sca-1)-positive macrophage population induced in the pathological conditions caused by lipopolysaccharide (LPS). Sca-1 is only upregulated in macrophages but not in monocytes and neutrophils upon LPS injection. Sca-1⁺ macrophages develop from resident peritoneal macrophages. LPS-induced Sca-1⁺ macrophage generation was partly blocked by anti–IFN–γ antibody, suggesting a role of IFN-γ in the process. LPS-stimulated production of IL-6, TNF-α, and CCL2 is significantly lower in Sca-1⁺ macrophages compared to their counterpart Sca-1^- macrophages. Depletion of Sca-1⁺ macrophages using anti-Sca-1 antibody significantly increased survival rate and reduced lung and kidney damage in an LPS-induced sepsis model. Taken together, we discovered a novel population of Sca-1⁺ macrophages in LPS-induced septic conditions.