Macrophages branch out

Research in mice reveals new roles for macrophages in shaping the development of the embryonic kidney.

Macrophages (red) and blood vessels (green) closely interact in the embryonic kidney. Image credit: Munro et al. 2019 (CC BY 4.0)

The kidneys clean our blood by filtering out waste products while ensuring that useful components, like nutrients, remain in the bloodstream. Blood enters the kidneys through a network of intricately arranged blood vessels, which associate closely with the ‘cleaning tubes’ that carry out filtration. Human kidneys start developing during the early phases of embryonic development. During this process, the newly forming blood vessels and cleaning tubes must grow in the right places for the adult kidney to work properly.

Macrophages are cells of the immune system that clear away foreign, diseased, or damaged cells. They are also thought to encourage growth of the developing kidney, but how exactly they do this has remained unknown. Munro et al. therefore wanted to find out when macrophages first appeared in the embryonic kidney and how they might help control their development.

Experiments using mice revealed that the first macrophages arrived in the kidney early during its development, alongside newly forming blood vessels. Further investigation using genetically modified mice that did not have macrophages revealed that these immune cells were needed at this stage to clear away misplaced kidney cells and help ‘set the scene’ for future development.

At later stages, macrophages in the kidney interacted closely with growing blood vessels. As well as producing molecules linked with blood vessel formation, the macrophages wrapped around the vessels themselves, sometimes even eating cells lining the vessels and the blood cells carried within them. These observations suggested that macrophages actively shaped the network of blood vessels developing within the kidneys. Experiments removing macrophages from kidney tissue confirmed this: in normal kidneys, the blood vessels grew into a continuous network, but in kidneys lacking macrophages, far fewer connections formed between the vessels.

This work sheds new light on how the complex structures in the adult kidney first arise and could be useful in future research. For example, adding macrophages to simplified, laboratory-grown ‘mini-kidneys’ could make them better models to study kidney growth, while patients suffering from kidney diseases might benefit from new drugs targeting macrophages.