Csf2, also known as colony-stimulating factor 2 or granulocyte-macrophage colony-stimulating factor (GM-CSF), is a cytokine that stimulates myeloid cells, such as dendritic cells and macrophages [2]. It is involved in multiple biological processes, including inflammation regulation, cell proliferation, and differentiation. The CSF2-STAT5 signaling pathway is one of the key associated pathways [4].

In disease-related studies, in antineutrophil cytoplasmic antibody-associated vasculitis (AAV), CCR2-/-chimeric mice (lacking classical monocytes) and CSF2rb-/-chimeric mice (deficient in CSF2 receptor subunit beta) were protected from necrotising crescentic glomerulonephritis (NCGN), indicating that Csf2 is a crucial pathological factor modulating monocyte pro-inflammatory functions and TH17 cell polarisation [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, showing Csf2's role in promoting alternative macrophage transition via the p-Stat5 pathway [3]. In gliomas, CSF2 knockdown or blockade of its signalling reduced microglia-dependent glioma invasion, and CSF2-depleted gliomas were smaller with less microglia and macrophages, suggesting tumour-derived Csf2 attracts and polarises microglia and macrophages to promote glioma progression [5].

In conclusion, Csf2 is essential in regulating inflammation, macrophage polarisation, and cell-cell interactions in the tumour microenvironment. Gene knockout mouse models have been instrumental in revealing its role in diseases like AAV, sepsis-induced acute kidney injury, and gliomas, providing insights into potential therapeutic strategies targeting Csf2 in these disease areas.

References:

1. Rousselle, Anthony, Sonnemann, Janis, Amann, Kerstin, Kettritz, Ralph, Schreiber, Adrian. 2022. CSF2-dependent monocyte education in the pathogenesis of ANCA-induced glomerulonephritis. In Annals of the rheumatic diseases, 81, 1162-1172. doi:10.1136/annrheumdis-2021-221984. https://pubmed.ncbi.nlm.nih.gov/35418479/

2. Saita, Kosuke, Moriuchi, Yuta, Iwagawa, Toshiro, Uchida, Kanji, Watanabe, Sumiko. 2022. Roles of CSF2 as a modulator of inflammation during retinal degeneration. In Cytokine, 158, 155996. doi:10.1016/j.cyto.2022.155996. https://pubmed.ncbi.nlm.nih.gov/35988458/

3. Li, Yiming, Zhai, Pan, Zheng, Yawen, Kellum, John A, Peng, Zhiyong. 2020. Csf2 Attenuated Sepsis-Induced Acute Kidney Injury by Promoting Alternative Macrophage Transition. In Frontiers in immunology, 11, 1415. doi:10.3389/fimmu.2020.01415. https://pubmed.ncbi.nlm.nih.gov/32733471/

4. . 2021. CSF2-STAT5 Signaling in TAMs Contributes to CSF1R Inhibition Resistance. In Cancer discovery, 12, OF2. doi:10.1158/2159-8290.CD-RW2021-155. https://pubmed.ncbi.nlm.nih.gov/34716187/

5. Sielska, Malgorzata, Przanowski, Piotr, Pasierbińska, Maria, Kettenmann, Helmut, Kaminska, Bozena. 2020. Tumour-derived CSF2/granulocyte macrophage colony stimulating factor controls myeloid cell accumulation and progression of gliomas. In British journal of cancer, 123, 438-448. doi:10.1038/s41416-020-0862-2. https://pubmed.ncbi.nlm.nih.gov/32390004/