Embryonic and adult-derived resident renal macrophages have different distribution and are maintained by distinctive mechanisms at steady state and during Inflammation

The mononuclear phagocytes, including macrophages, dendritic cells and monocytes, are present in the kidney and are greatly involved in the pathogenesis of most kidney diseases. However, it is difficult to discriminate them from each other in the kidney, partly due to the fact that the markers generally used to discriminate them in other organs, such as CD11c, MHC class II and CX3CR1, are highly expressed by many of them. Here, we developed a strategy of multicolor flow cytometry to clearly differentiate them and their subtypes. Their identities were further confirmed by fate mapping, function analyses and lineage‐specific depletion. Using this strategy, we were able to show their inflammatory kinetics and activation alteration in a murine model of renal ischemia‐reperfusion injury. Moreover, by lineage tracing, we found that in adult mice, there were about 25% renal macrophages derived from embryo which are self‐maintaining, while other macrophages were actively replenished from the bone marrow. The embryonic and adult‐derived macrophages were distinctive in transcriptome and in distributions, as the embryonic macrophages highly accumulated in the medulla. Renal epithelial cells highly express CX3CL1 and the CX3CL1‐CX3CR1 axis was required for the differentiation of monoctes to the adult‐derived macrophages but not for the recruitment of monocytes from blood into the kidney. Thus, our discriminating strategy can be widely exploited to analyze mononuclear phagocytes in the kidney and has unveiled the specificity of turnover of renal macrophages. Support or Funding Information National Natural Science Foundation of China (Grant# 81670378, 81700365 and 31771266)