Transitioning from the womb to the outside world is a crucial developmental period for mammals, requiring various physiological systems to adapt.
Of these, the immune system plays a particularly pivotal role in growth, organ maturation and defence against pathogens.
A new study led by Mater Research and The University of Queensland’s Professor David Hume AO has explored the importance of macrophages—specialised immune cells that are essential for tissue development and repair—and how their function can be disrupted by mutations in the colony-stimulating factor 1 receptor (CSF1R) gene.
The research team explored how these disruptions can lead to severe developmental abnormalities and looked at potential therapeutic solutions.
A homozygous mutation CSF1R gene (Csf1rko) occurs when two identical mutated copies of a gene are inherited from each parent, leading to a genetic disorder or trait. The effects of this were examined in pre-clinical models, showing that Csf1rko resulted in a complete absence of macrophages, causing impaired organ development, growth failure and early mortality.
Prof Hume, who leads the Macrophage Biology Research group, said that by analysing the molecular consequences of macrophage deficiency, the team aimed to uncover the mechanisms through which macrophages influence postnatal development and systemic homeostasis.
“We found that the absence of macrophages led to subtle but significant changes in gene expression across all major organs,” Prof Hume said.
To counteract these effects, the researchers explored wild-type bone marrow transplantation (BMT) as a potential therapeutic approach to restore macrophage populations. This healthy and unmodified bone marrow was found to successfully reverse many of the developmental defects, leading to improved growth, organ function and survival, however not all macrophage populations were fully restored.
“In the brain, bone marrow derived microglia-like cells exhibited distinct expression profiles compared to native microglia, suggesting that some tissue-specific macrophages cannot be completely replaced through BMT,” Prof Hume said.
“Understanding the role of macrophages in postnatal development may inform therapeutic approaches for conditions affecting premature or low-birth-weight infants, who are at high risk for immune-related complications.”
“The successful restoration of macrophage populations through BMT in pre-clinical models raises the possibility of similar interventions to treat rare human macrophage deficiencies, including CSF1R mutations.”
This study also highlights the potential of CSF1 as a treatment to promote innate immune development in premature or low birth weight infants.
The full paper, titled “Wild-type bone marrow cells repopulate tissue resident macrophages and reverse the impacts of homozygous CSF1R mutation” was published in PLOS Genetics in January 2025.
