Phagocytes Are Formed Independently

Monocytes, macrophages derived from them, and dendritic cells are important parts of the innate immune system. They defend the body against microbes, support the adaptive immune system, and make sure that defective cells do not accumulate in the various tissues of the body.

On the other hand, monocytes and macrophages also promote a number of pathogenic, inflammatory processes such as type 2 diabetes and arteriosclerosis. Chemical messengers secreted by the cells contribute to prolonging inflammatory reactions that may become dangerous, for example by leading to arteriosclerosis.

“Tumor-associated macrophages in particular are a problem in cancer,” says DKFZ’s Markus Feuerer. “Normally they are programmed for wound healing. Hence they let new blood vessels sprout, suppress the immune response, and produce growth factors that can give an additional boost to tumor growth. They also promote tumor metastasis.”

These effects have led clinicians to try to find ways to selectively switch off monocytes and macrophages using drugs. While doing so, they need to avoid targeting the closely related dendritic cells. Discoveries about the biology of all three types of cells might show how to target the first two without affecting the third. One possibility is to switch off monocytes and macrophages right when they are formed. In hopes of doing so, Markus Feuerer and his team first needed a better understanding of how these cells develop in the bone marrow.

Monocytes, macrophages and dendritic cells originate from a common progenitor cell called MDP (monocyte/macrophage-dendritic cell precursor) in the bone marrow. MDPs can develop into either dendritic cells or monocytes. So far, however, the process of differentiation into the latter type has been unclear.

In mice, Markus Feuerer and his coworkers have now shown that monocytes develop from a special progenitor of their own (called “cMoP”) from the MDP. cMoP cells strongly proliferate and specifically develop into monocytes and macrophages, but not into dendritic cells.

In their article, Feuerer’s team made a detailed analysis of the molecular differences between monocytes and their progenitors.”Monocyte progenitors may be an interesting drug target, because targeting them could thus inhibit the macrophage population early on without impairing dendritic cells and their important functions in immune defense,” says Feuerer, an immunologist.

Jan Hettinger, David M. Richards, Jenny Hansson, Melanie M. Barra, Ann-Cathrin Joschko, Jeroen Krijgsveld and Markus Feuerer: Origin of monocytes and macrophages in a committed progenitor. Nature Immunology 2013, DOI: 10.1038/ni.2638