The researchers have discovered a new type of immune cell that helps to keep breast tissue healthy by regulating a vital process within mammary ducts - the sites where milk is produced and transported, but also where most breast cancers arise.

Using advanced three-dimensional (3D) imaging techniques, the team observed how the immune cells called ductal macrophages monitor for threats in the mammary ducts and help to maintain tissue health by 'eating' up dying milk-producing cells needing to be cleared away once lactation stops. It was published today in the journal Nature Cell Biology.

The mammary gland is a dynamic organ that undergoes dramatic remodelling throughout life. The branching ducts bloom to form milk-producing 'factories' in lactation, which must be eliminated once lactation stops. Mammary ducts are of particular interest to breast cancer researchers because this site is prone to cancer development.

While exploring mammary ducts using high-resolution imaging techniques, the researchers were surprised to discover a new immune cell type, and its specific role in maintaining healthy, intact breast tissue.

Although initially originating from embryonic precursors, ductal macrophages derive from circulating monocytes as they expand during puberty. Moreover, they undergo proliferation in pregnancy to maintain complete coverage of the epithelium in lactation, when they are poised to phagocytose milk-producing cells post-lactation and facilitate remodelling.

Interestingly, ductal macrophages strongly resemble mammary tumor macrophages and form a network that pervades the tumor. Thus, the mammary epithelium programs specialized resident macrophages in both physiological and tumorigenic contexts.

"We were excited to find that these cells play an essential role at a pivotal point in mammary gland function called involution when lactation stops, milk-producing cells die and breast tissue needs to remodel back to its original state. We watched incredulously as the star-shaped ductal macrophages probed with their arms and ate away at dying cells. The clearing action performed by ductal macrophages helps redundant milk-producing structures to collapse, allowing them to successfully return to a resting state," the senior author said.

When the researchers later removed ductal macrophages from the mammary ducts they discovered that no other immune cells were able to swiftly carry out this essential process.

Most organs in the body including the brain, liver, lung, skin and intestine have their own population of macrophages - a name of Greek origin that means 'big eater'. These cells play important roles in regulating infection, inflammation and organ function within their sites of residence.

The author said that going forward, the team hoped to explore the function of ductal macrophages at different stages of mammary gland development, such as the transitions into adulthood and pregnancy.

"We also want investigate the role that these duct-specific immune cells play in helping cancer to grow and spread," the senior author said.

https://www.wehi.edu.au/news/new-type-immune-cell-discovered-breast-ducts

https://www.nature.com/articles/s41556-020-0505-0