Human peritoneal CCR2LowCRIgHigh macrophage subset exhibits embryonic origin-like phenotypes

maintained by the differentiation of bone marrow-derived monocytes and the proliferation of macrophages originating from yolk sac or fetal liver. However, to what extent this paradigm shift is the case for human tissues is not fully understood. Here, we detect a human peritoneal macrophage subset which exhibits embryonic origin-like phenotypes. Macrophages in ascites of patients with gastric cancers were divided into CCR2Low and CCR2High subsets, the ratio of which was variable among donors. The gene expression profiles of these subsets were similar to those of macrophage subsets in hearts. CRIg was recently reported as a marker to distinguish two macrophage subsets in ascites of patients with cirrhosis. CCR2Low and CCR2High subsets identified in this study expressed CRIg at high and low levels, respectively. Importantly, the CCR2LowCRIgHigh subset expressed the cell proliferation marker Ki67 and recently-proposed core markers for macrophages with embryonic origin (TIMD4, LYVE1, and FOLR2) at higher levels than those of the CCR2HighCRIgLow subset. Moreover, many other markers shared by TIMD4+LYVE1+FOLR2+ macrophages in heart, lung, kidney and liver exhibited a similar expression pattern in the peritoneal CCR2LowCRIgHigh subset. These results suggest that the CCR2LowCRIgHigh subset in peritoneal cavity contains macrophages with embryonic origin.