Csf2, also known as colony-stimulating factor 2 or granulocyte-macrophage colony-stimulating factor (GM-CSF), is a cytokine that stimulates myeloid cells like dendritic cells and macrophages. It plays a role in various biological processes such as inflammation regulation and cell growth. The signaling pathways it is associated with include Akt/Mtor, p-Stat5, Stat3, and Notch, influencing important cellular functions and disease-related mechanisms [2,3,4,5].

In ANCA-induced glomerulonephritis, CCR2 -/- chimeric mice with reduced circulating classical monocytes (CMs) and CSF2rb -/- chimeric mice with fewer kidney TH17 cells were protected from the disease, indicating that CSF2 is crucial for inducing kidney damage by modulating monocyte pro-inflammatory functions and TH17 cell polarization [1]. In sepsis-induced acute kidney injury, intraperitoneal injection of a Csf2-neutralizing antibody after cecal ligation and puncture (CLP) aggravated kidney injury, while administration of recombinant mouse Csf2 protein rescued mice, suggesting Csf2 promotes alternative macrophage transition and plays a critical role in regulating macrophage transition via activation of p-STAT5 [3]. In gliomas, CSF2-deficient human glioma cells failed to attract microglia, and CSF2-depleted gliomas were smaller, attracted fewer microglia and macrophages, and provided a survival benefit in tumour-bearing mice, indicating that tumour-derived CSF2 attracts and polarizes microglia and macrophages to support tumour progression [6].

In conclusion, Csf2 has essential functions in inflammation, macrophage regulation, and cell-cell interactions in the context of various diseases. Gene-knockout mouse models, such as those in ANCA-induced glomerulonephritis, sepsis-induced acute kidney injury, and gliomas, have been instrumental in revealing its role in disease pathogenesis, providing potential therapeutic targets for these conditions.