CSF1 Gene

CSF is an acronym for "colony stimulating factor 1". The CSF1 gene is a protein coding gene located on chromosome 1p13.3. The CSF1 gene encodes a protein(CD115) is present in its active extracellular form as a disulfide-linked homodimer and is thought to be formed by proteolytic cleavage of membrane-bound precursors.

CD115 plays an essential role in regulating the survival, proliferation, and differentiation of hematopoietic progenitor cells, particularly mononuclear phagocytes such as macrophages and monocytes. The cytokine promotes the release of proinflammatory chemokines and thus plays an important role in innate immunity and inflammatory processes. CD115 Plays an important role in the regulation of osteoclast proliferation and differentiation as well as in the regulation of bone resorption and is required for normal bone development.

The encoded protein may be involved in placental development. Alternative splicing results in multiple transcript variants. Diseases associated with CSF1 include:

• pigmented villonodular synovitis
• and
• tenosynovial giant cell tumor.

Related metabolic pathways include innate immune system and PEDF-induced signal transduction. Activities associated with this gene include protein homodimerization activity and growth factor activity.

Cytokine is required for normal fertility in males and females.

Promotes actin cytoskeleton reorganization, regulates cell adhesion and cell migration. Plays a role in lipoprotein clearance.

Inflammation: Colony-stimulating factor 1 (CSF1) and interleukin-34 (IL34) act as ligands to control macrophage differentiation via the CSF1 receptor (Lin W et al 2019). Animal experiments have established their role in macrophage differentiation by neutralizing CSF1 and/or IL34, particularly in stationary microglia, Langerhans cells, and renal macrophages. IL34 and CSF1 play a non-redundant role in macrophage differentiation. Thus, therapeutic intervention targeting IL34 and/or CSF1 may be an effective treatment for macrophage-related immunopathies (Lin W et al. 2019). IL-34 and colony-stimulating factor 1 (CSF1) are two alternative ligands for the CSF1 receptor that play non-redundant roles in the development, survival, and function of tissue macrophages and Langerhans cells (LCs) (Wang Y et al. 2016).

However, during UV-induced skin damage, the regeneration of LCs depends on neutrophil granulocytes entering the skin, which produced large amounts of CSF1. (Wang Y et al 2016).

Oncology: The association between macrophage colony-stimulating factor-1 receptor (CSF-1R) expression and prognosis of cancer patients has been investigated in several studies (Mo H et al. 2021). Pooled analysis showed that overexpression of CSF-1R was significantly associated with worse PFS and OS. Overexpression of CSF-1R thus appears to be a predictor of worse prognosis in patients with various malignancies, particularly hematologic malignancies, suggesting that it may be a potential biomarker for predicting cancer survival and a potential molecular target in the treatment of malignancies (Mo H et al. 2021).

1. Lin W et al (2019) Function of CSF1 and IL34 in macrophage homeostasis, inflammation, and cancer. Front Immunol 10:2019. doi: 10.3389/fimmu.2019.02019
2. Mo H et al. (2021) Overexpression of macrophage-colony stimulating factor-1 receptor as a prognostic factor for survival in cancer: A systematic review and meta-analysis. Medicine (Baltimore) 100:e25218.
3. Wang Y et al. (2016) Nonredundant roles of keratinocyte-derived IL-34 and neutrophil-derived CSF1 in Langerhans cell renewal in the steady state and during inflammation. Eur J Immunol 46:552-559.