CSF1

CSF1, or colony-stimulating factor 1, also known as macrophage colony-stimulating factor (M-CSF), is a cytokine that regulates the survival, proliferation, and differentiation of cells in the monocyte/macrophage lineage. It is encoded by the CSF1 gene and exists in multiple isoforms produced by alternative splicing, including a secreted glycoprotein and a membrane-bound form. CSF1 signals through the CSF1 receptor (CSF1R or c-FMS), a receptor tyrosine kinase expressed on macrophage-lineage cells. Binding activates signaling pathways such as PI3K-AKT, MAPK-ERK, and JAK-STAT, promoting cell survival, proliferation, and maturation, as well as influencing macrophage function and recruitment.

CSF1 is produced by a variety of cell types, including osteoblasts, fibroblasts, endothelial cells, adipocytes, and certain tumor cells, and its expression can be regulated by inflammatory signals, hormones, and the tissue microenvironment. In development and tissue homeostasis, CSF1 supports the mononuclear phagocyte system, osteoclast formation, placental development, and mammary gland development, and it participates in wound healing and immune responses.

Clinical and research relevance centers on the CSF1/CSF1R axis as a therapeutic target. Deficiency of CSF1 signaling in mice (the op/op model) leads to reduced macrophages, osteopetrosis, and impaired mammary development. In humans, modulation of CSF1/CSF1R is explored in cancer and inflammatory diseases; CSF1R inhibitors, such as pexidartinib, are used to reduce tumor-associated macrophages in certain conditions, while altering CSF1 signaling can impact bone remodeling and immune function.