New study shows that a specific growth factor causes early-stage immune cells (macrophage precursors) to ‘drink’, which activates a special enzyme. This cell drinking and enzyme activation determines whether early-stage macrophages turn into ‘grown up’ macrophages or a completely different immune cell, called a neutrophil. Macrophages are extraordinary immune cells that are essential for life, especially mammalian development. They work a bit like master regulators, keeping the body’s tissues balanced and healthy. Scientists know that macrophages develop from earlier-stage (precursor) cells, but don’t entirely know how. They do know that their development needs the presence of a special protein called macrophage growth stimulating factor (called M-CSF). Macrophages are present in all tissues and organs and are involved in organ development, protecting tissues from infections, and helping repair and regenerate damaged tissues. Here, we explain a major mechanism of macrophage development which impacts tissue formation. Dr Chris Lucas IRR Group Leader Growth factor M-CSF causes early-stage macrophages to ‘drink’, which activates enzyme Wnk1IRR Group Leader Chris Lucas working with colleagues from New York, Iowa and Oklahoma, studied the links between M-CSF and the enzyme Wnk1 in macrophage development, as they had recently discovered that Wnk1 has crucial functions in mature macrophages when they eat dying cells. Unexpectedly, they found that M-CSF caused early-stage macrophages to undergo ‘cell drinking’, where cells internalise fluid and nutrients from their environment. This in turn, activated enzyme Wnk1.Cell drinking and enzyme activation determines which immune cells these early-stage macrophages turn intoTogether, the cell drinking and activated Wnk1 enzyme, caused early-stage macrophages to turn into mature macrophages. To the researchers’ surprise, when Wnk1 activity or cell drinking was inhibited, these early-stage macrophages turned into a different immune cell type called a neutrophil. Researchers also found that mice lacking Wnk1 in early-stage macrophages during development, were born small, with disrupted and underdeveloped major internal organs. Macrophage precursor cells over time undergoing cell drinking, observable by the internalisation of pink fluid from outside the cell into small pink circular ‘bubbles’ and highlighted in the magnified image. The researchers mainly studied Wnk1 and cell drinking by macrophage precursors in the context of macrophage and organ development. Whether these same pathways are involved in tissue infections, and the repair of organs after injury, are ongoing lines of study.Read the full paper in 'Nature Communications’Lucas research groupPerry research group Tags CIR Publication date 28 May, 2025
