Human peritoneal CCR2^LowCRIg^High macrophage subset exhibits embryonic origin-like phenotypes

Recent studies in mouse models have demonstrated that macrophages in adult tissues are maintained not only by the differentiation of bone marrow-derived monocytes but also by the proliferation of macrophages originating from the yolk sac or fetal liver. However, the extent to which this paradigm shift occurs in human tissues is not fully understood. In this study, we detected a human peritoneal macrophage subset that exhibited embryonic origin-like phenotypes. Macrophages in the ascites of patients with gastric cancer were divided into CCR2^Low and CCR2^High subsets, the ratios of which varied among donors. The gene expression profiles of these subsets were similar to those of the macrophage subsets in the heart. CRIg was recently reported as a marker for distinguishing between two macrophage subsets in the ascites of patients with cirrhosis. CCR2^Low and CCR2^High subsets expressed high and low levels of CRIg, respectively. Importantly, the CCR2^LowCRIg^High subset expressed the cell proliferation marker Ki67 and the recently proposed core markers (TIMD4, LYVE1, and FOLR2) of embryo-derived macrophages at higher levels than the CCR2^HighCRIg^Low subset. Moreover, many other markers shared by TIMD4⁺LYVE1⁺FOLR2⁺ macrophages in heart, lung, kidney, and liver exhibited similar expression patterns in the peritoneal CCR2^LowCRIg^High subset. These results suggest that the CCR2^LowCRIg^High subset in the peritoneal cavity contains macrophages with embryonic origin.