Immune cells do more than fight infections – they are essential for proper tooth development and regeneration

Macrophages are white blood cells that typically engulf bacteria, remove dead cells and help repair damaged tissues. In recent years, research has also focused on their role in tissue biology and on how they influence the function of various organs – how they regulate their development, support regeneration and interact with stem cells. Scientists from the Faculty of Medicine at Masaryk University are the first to describe their crucial role in tooth development.

“Macrophages populate developing tooth germs as early as the initial stages of embryonic development, and their numbers increase significantly during the period before teeth erupt,” explains Jan Křivánek, whose team in Brno has been studying the tooth ecosystem for many years. To do so, they use mouse models whose incisors continuously grow throughout their lives, as well as molars that are similar to human teeth.

“The continuous renewal of incisors is driven by stem cells that remain active in these teeth throughout life. As we have shown, macrophages reside in the immediate vicinity of these stem cells,” Křivánek adds. “Our experiments demonstrated that when we selectively remove macrophages from these tissues using genetic and pharmacological approaches, normal tooth development is disrupted, as is the teeth’s ability to continuously regenerate.”

The removal of macrophages resulted in severe developmental defects – ranging from abnormalities in the number, arrangement and shape of teeth, to impaired tooth eruption and the development of malformed tooth roots. Similarly adverse effects were observed when macrophages were removed from already developed teeth, where their depletion in continuously growing incisors led to a surprisingly rapid and dramatic disruption of dentin and enamel formation.

According to the researchers, the finding that some of these defects can be reversed is also important. “Following bone marrow transplantation, macrophages were restored in the environment of the developing teeth in genetically affected animals,” explains Marcos González López, one of Křivánek’s PhD students and the first author of the study, who now continues his research into tissue regeneration in Gothenburg, Sweden. “Specifically, these were so-called M2 macrophages, which are known for their ability to support tissue repair.”

Published in the prestigious journal Nature Communications, the study provides further evidence that the role of macrophages extends far beyond the traditional view of them as cells serving primarily an immune function. It demonstrates that these cells actively coordinate the activity of cells that are crucial for tooth development, opening up new avenues of research into tooth regeneration and the development of biological therapies that could one day help patients with developmental disorders of the teeth, dental damage or tooth loss.