Characterizing the function and origin of kidney capsule macrophages

Macrophages are a type of innate immune cell that have roles in pathogen detection, homeostasis, tissue development, and inflammation. These cells can be localized to tissues and self-renewing, or recruited from the bone marrow via a monocyte intermediate. Three main subsets of tissue resident macrophages were previously described with conserved ontogeny and self-renewal capacity across tissues. These subsets include TLF+ (TIMD4+ LYVE1+FOLR2+), MHCIIhi, and CCR2+. The kidney parenchyma is notably lacking the TLF+ macrophages that are present in all other tissues and constitute a yolk-sac derived subset, capable of self-renewal and contributing to wound repair. The kidney capsule is a fibrous tissue that encapsulates the kidney parenchyma, that remains vastly understudied. It was recently shown that the kidney capsule contains TLF+ macrophages, however the function and origin of this population within the capsule remains unknown. Here, with flow cytometry and immunofluorescence staining, we further cement this population as a discrete population independent of kidney parenchymal macrophages. We characterize the self-renewal capacity of kidney capsule macrophages, describe a specific role for fibroblast-derived macrophage colony stimulating factor (mCSF) in the survival of capsule (and not parenchyma) macrophages; and show that they are heavily localized in clusters throughout the capsule based on their origin. Future work will explore the functional role of these cells in the context of acute kidney injury.