Abstract
Renal macrophages (RMs) participate in tissue homeostasis, inflammation and repair. RMs consist of embryo-derived (EMRMs) and bone marrow-derived RMs (BMRMs), but the fate, dynamics, replenishment, functions and metabolic states of these two RM populations remain unclear. Here we investigate and characterize RMs at different ages by conditionally labeling and ablating RMs populations in several transgenic lines. We find that RMs expand and mature in parallel with renal growth after birth, and are mainly derived from fetal liver monocytes before birth, but self-maintain through adulthood with contribution from peripheral monocytes. Moreover, after the RMs niche is emptied, peripheral monocytes rapidly differentiate into BMRMs, with the CX3CR1/CX3CL1 signaling axis being essential for the maintenance and regeneration of both EMRMs and BMRMs. Lastly, we show that EMRMs have a higher capacity for scavenging immune complex, and are more sensitive to immune challenge than BMRMs, with this difference associated with their distinct glycolytic capacities.
Highlights
Renal macrophages (RMs) participate in tissue homeostasis, inflammation and repair
We found that RMs from neonate (P1) and juveniles (P21) had a higher percentage of Ki67+ stained cells than RMs from adults (P56 and P91), which shows that RMs proliferate rapidly in early life (Fig. 1d and Supplementary Fig. 1b)
We investigated the fate of embryo-derived renal macrophages (EMRMs) in further detail and explored how bone marrow (BM)-derived monocytes contribute to the pool of RMs at different developmental stages
Summary
RMs consist of embryo-derived (EMRMs) and bone marrow-derived RMs (BMRMs), but the fate, dynamics, replenishment, functions and metabolic states of these two RM populations remain unclear. RMs account for about 50% of total CD45+ leukocytes in mouse kidney and are found in large numbers in human kidney[3] They consist of embryo-derived (EMRMs) and bone marrowderived RMs (BMRMs)[1], but their fate, dynamics, and replenishment have not been systematically investigated[1,2]. Whether these two populations have different functions and metabolic states remains unclear[1,2]. Another study in colon cancer showed significantly greater expansion of embryo-derived macrophages, as compared to those derived from BM, during tumor progression, suggesting those cells may support tumor development[11]
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