Genetic switch MafB enables macrophages to reach full maturity and preserve organ health

Researchers at the University of Liège have identified a key genetic regulator that enables macrophages to reach full maturity and preserve the health of our organs. The MafB factor, a veritable "molecular switch", activates or deactivates certain genes at the right time and in the right place, leading to the production of macrophages responsible for defending our body and supporting the functioning of our organs. Without MafB, macrophages can become dysfunctional, no longer performing their beneficial roles properly. 

Macrophages are essential immune cells found in almost all tissues of the body. Often described as the body's 'cleaning and maintenance team', macrophages eliminate pathogens (biological agents capable of causing disease in a host organism), remove dead cells and debris from tissues, recycle materials such as iron, and contribute to the normal functioning of tissues. While macrophages adapt to the specific needs of each organ, they also share a common identity that enables them to perform these fundamental functions. Until now, scientists did not fully understand how this shared identity is maintained between different tissues and even between different species. In a new study led by Professor Thomas Marichal of the Immunophysiology Laboratory (ULiège),a team of researchers has discovered that a transcription factor called MafB acts as a central genetic switch that enables macrophages to become fully functional. When monocytes (immature precursor cells) transform into tissue macrophages, MafB levels gradually increase, guiding this maturation process. In the absence of MafB, macrophages remain stuck in an immature state and cannot properly perform their protective roles in tissues. "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."

At the molecular level, MafB controls a vast network of genes involved in key macrophage functions, including phagocytosis (the ability to engulf harmful particles and cellular debris) and the maintenance of tissue homeostasis. The study shows that this regulatory programme is remarkably conserved from mice to humans, and even across vertebrates, highlighting its fundamental importance in biology. Importantly, the consequences of losing this programme extend beyond the immune system alone. The researchers found that impaired macrophage maturation affects several organs, leading to defects in processes such as iron recycling in the spleen, as well as in the functioning of the lungs, intestines and kidneys. This illustrates how profoundly macrophages contribute to the overall physiological balance of the body.

These results reveal that a shared genetic programme conserved throughout evolution underlies the specialization of macrophages across tissues. This explains how these cells can adapt to different organs while preserving their fundamental identity."

Domien Vanneste, first author of the scientific article

Beyond fundamental biology, this discovery opens up new perspectives for medicine. Many chronic diseases, including inflammatory disorders, fibrosis, infections, and metabolic diseases, involve dysfunctional macrophages. Targeting MafB or the pathways it controls could offer innovative strategies for restoring proper macrophage function and improving tissue health in a wide range of pathologies. Overall, this work identifies MafB as a central and conserved regulator of macrophage development, identity, and function, shedding new light on how the immune system sustainably protects the health of multiple organs.