Csf3, also known as colony-stimulating factor 3 or G-CSF, is a crucial cytokine. It plays a key role in neutrophil production and function, stimulating the maturation, proliferation, and trafficking of myeloid progenitor cells. It is involved in the cytokine-cytokine receptor interaction pathway and is of great biological importance in immune-related processes [1,2,4]. Genetic models, such as gene knockout mouse models, have been valuable in studying its functions.

In human 'knockouts' of CSF3, patients from two families with biallelic inactivating variants in CSF3 presented with severe congenital neutropenia (SCN), mirroring the phenotype seen in mouse and zebrafish models of CSF3 deficiency, suggesting that CSF3 deficiency in humans causes a novel autosomal recessive form of SCN [1]. In a mouse model of acute exacerbation of pulmonary fibrosis (AE-PF), exogenous administration of CSF3 protein exacerbated AE-PF. Mechanistically, CSF3 disrupted alveolar epithelial barrier integrity via the PI3K/p-Akt/Snail pathway [3].

In conclusion, CSF3 is essential for neutrophil-related functions. Gene knockout models have revealed its role in severe congenital neutropenia and the exacerbation of pulmonary fibrosis. Understanding CSF3's functions through these models provides insights into the pathogenesis of related diseases, which may help in developing new therapeutic strategies for these conditions.

References:

1. Khouj, Ebtissal, Marafi, Dana, Aljamal, Bayan, Awaji, Ali, Alkuraya, Fowzan S. 2023. Human 'knockouts' of CSF3 display severe congenital neutropenia. In British journal of haematology, 203, 477-480. doi:10.1111/bjh.19054. https://pubmed.ncbi.nlm.nih.gov/37612131/

2. Cai, Wei, Hu, Mengyan, Li, Chunyi, Lu, Yan, Lu, Zhengqi. 2022. FOXP3+ macrophage represses acute ischemic stroke-induced neural inflammation. In Autophagy, 19, 1144-1163. doi:10.1080/15548627.2022.2116833. https://pubmed.ncbi.nlm.nih.gov/36170234/

3. Guo, Bingnan, Liu, Wenwen, Ji, Xuan, Yan, Xianliang, Chen, Bi. 2024. CSF3 aggravates acute exacerbation of pulmonary fibrosis by disrupting alveolar epithelial barrier integrity. In International immunopharmacology, 135, 112322. doi:10.1016/j.intimp.2024.112322. https://pubmed.ncbi.nlm.nih.gov/38788452/

4. Xu, Junfeng, Li, Na, Xie, Hui, Yang, Lang, Jin, Peng. 2025. CSF3 promotes colorectal cancer progression by activating p65/NF-κB signaling pathway and inducing an immunosuppressive microenvironment. In Translational oncology, 53, 102310. doi:10.1016/j.tranon.2025.102310. https://pubmed.ncbi.nlm.nih.gov/39929064/