Macrophages are essential players in the immune system, responsible for combating infections and facilitating tissue repair. However, the complexity of these cells has made it difficult to study their activation processes, which is crucial for developing new therapeutics. A recent study has made significant strides in this area by identifying a reliable marker and developing new tools to study macrophage activation.

Researchers from the University of Surrey discovered that the protein colony stimulating factor 1 receptor (CSF1R) serves as a dependable marker for monocytes and dendritic cells in blood, as well as macrophages in tissues. This breakthrough allows for the clear identification and separation of different cell types across all ages and sexes.

According to Fernando Martinez Estrada, senior author on the study published in Cell Reports, “We have developed a method using CSF1R that can identify all types of mononuclear phagocyte system cells in the body. This marker is incredibly useful for studying these cells in both health and disease, and it unlocks exciting new possibilities for cell isolation and quantification for diagnosing and monitoring various conditions with a single cell marker.”

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The study also introduced a set of tools to analyze how immune cells respond to various signals, such as IL-4 (healing and fibrosis), steroids (deactivation), IFNγ (infection fighting), and LPS (inflammation). A novel concept termed Macrophage Activation Mosaicism was described, indicating that macrophages can exhibit a mix of activation characteristics rather than switching between two canonical states.

“Recognising that macrophages can have mixed activation status helps us better understand their roles in different diseases and could lead to more targeted and effective treatments,” explained Federica Orsenigo, co-author of the study.

Siamon Gordon, another co-author, added: “Therapies that seek to re-educate macrophages are widely sought. However, the tools to measure activation are underdeveloped. Having a robust multi-gene tool to study macrophage activation can help in drug screening, identify drugs that revert macrophage activation, and eventually help with patient characterisation and personalised medicine.”