Macrophages are key immune cells found in nearly every tissue. Often described as the body’s ‘cleaning and maintenance team’, they destroy pathogens (biological agents capable of causing disease in a host organism), clear away dead cells and debris, recycle materials such as iron, and help tissues function normally. Although macrophages tailor their behavior to the needs of each organ, they share a core identity that allows them to perform these essential tasks. Until recently, researchers did not fully understand how this shared identity is preserved across different tissues and even across species.

In research led by Professor Thomas Marichal of the Immunophysiology Laboratory (ULiège), scientists discovered that MafB, a transcription factor, serves as a central genetic switch that guides macrophages toward full functionality. As monocytes (immature precursor cells) develop into tissue macrophages, levels of MafB steadily rise, directing the maturation process. Without MafB, macrophages remain in an immature state and are unable to properly protect the tissues where they reside. “Our results show that MafB functions as a master regulator that gives macrophages their identity and equips them with the capabilities necessary to support organ health,” explains immunologist Thomas Marichal. “Without this instruction programme, these cells are present but not fully operational.”

Conserved Genetic Program Across Species

At the molecular level, MafB governs a broad network of genes that control critical macrophage activities, including phagocytosis (the ability to engulf harmful particles and cellular debris) and the maintenance of tissue homeostasis. The researchers found that this regulatory program is highly conserved from mice to humans and across vertebrates, emphasizing its fundamental biological importance.

The effects of losing this genetic program extend beyond immune defense alone. The team observed that disrupted macrophage maturation can impact multiple organs. Problems were seen in iron recycling within the spleen and in the normal functioning of the lungs, intestines and kidneys. These findings demonstrate how deeply macrophages contribute to the body’s overall physiological balance. “These results reveal that a shared genetic programme conserved throughout evolution underlies the specialisation of macrophages across tissues,” adds Domien Vanneste, first author of the scientific article. “This explains how these cells can adapt to different organs while preserving their fundamental identity.”

Implications for Chronic Disease and Treatment

The discovery has important medical implications. Dysfunctional macrophages play a role in many chronic conditions, including inflammatory disorders, fibrosis, infections, and metabolic diseases. By targeting MafB or the biological pathways it regulates, researchers may be able to restore healthy macrophage function and improve tissue health across a range of diseases.

Overall, the findings establish MafB as a central and evolutionarily conserved regulator of macrophage development, identity, and function, offering new insight into how the immune system helps protect and sustain the health of multiple organs.