Available evidence suggests that macrophages can promote the growth and maintenance of renal tissue; however, the exact origin and roles of macrophages in the developing kidney are unclear. New findings suggest that macrophages have dual roles in defining the metanephric field and in promoting vascular connectivity in the developing kidney. “Our findings indicate that macrophages prune the rostral domain of the early nephron progenitor population,” says David Munro. “In addition, deletion of macrophages resulted in fewer connections being formed between blood vessels, suggesting that macrophages are involved in shaping the network of blood vessels in the developing kidney.”

Credit: Lara Crow/Springer Nature Limited

Using imaging to characterize macrophage distribution, the researchers show that macrophages localize near the metanephric mesenchyme as it condenses at the caudal aspect of the Wolffian duct. However, these macrophages largely avoid the caudal metanephric mesenchyme and instead mainly localize alongside rostral clusters of SIX2+ nephron progenitor cells, where the researchers propose they might clear rostral SIX2+ cells. In support of this hypothesis, deletion of macrophages led to persistence of rostral nephrogenic progenitors and delayed ureteric bud development.

deletion of macrophages resulted in fewer connections being formed between blood vessels

The researchers further showed that the developing kidney contains both an early population of macrophages and a later-arriving population of myeloid cells. Imaging studies showed macrophages interacting with the developing renal vasculature. “A surprisingly high percentage of macrophages were wrapped around newly forming blood vessels,” explains Munro. Single-cell RNA sequencing showed that in addition to being enriched for mRNAs linked to phagocytosis, kidney macrophages expressed mRNAs linked to vasculature development. Finally, the researchers showed that depleting macrophages induced higher numbers of unconnected endothelial structures, demonstrating a role for the macrophages in the production or maintenance of endothelial connections in the developing kidney.