Csf2ra, the gene encoding the alpha subunit of the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor, is a key member of the hematopoietic receptor superfamily in myeloid cells. It activates receptor-associated JAK and STAT proteins, playing a crucial role in GM-CSF signaling pathway, which is involved in multiple biological processes such as cell survival, differentiation, and immune response [1,2].

In a murine model, homozygous disruption of Csf2ra (Csf2ra-/-mice) led to a phenotype similar to human hereditary pulmonary alveolar proteinosis (hPAP), with impaired GM-CSF-dependent surfactant clearance by alveolar macrophages, resulting in surfactant accumulation and respiratory failure. This indicates Csf2ra is essential for normal alveolar macrophage function in maintaining lung homeostasis [4]. Also, deletion of Csf2ra in mice attenuated acute lung injuries induced by intratracheal inoculation of aerosolized ricin, likely through reducing the pro-inflammatory response [3].

In conclusion, Csf2ra is vital for GM-CSF signaling and normal alveolar macrophage function. Gene-knockout mouse models of Csf2ra have provided valuable insights into its role in lung-related diseases, such as hPAP and acute lung injury, highlighting its potential as a therapeutic target in these disease areas.

References:

1. Gao, Qi, Yang, Yunlong, Luo, Yizhuo, Lu, Gang, Gong, Lang. 2023. African Swine Fever Virus Envelope Glycoprotein CD2v Interacts with Host CSF2RA to Regulate the JAK2-STAT3 Pathway and Inhibit Apoptosis to Facilitate Virus Replication. In Journal of virology, 97, e0188922. doi:10.1128/jvi.01889-22. https://pubmed.ncbi.nlm.nih.gov/37022174/

2. Trapnell, Bruce C, Nakata, Koh, Bonella, Francesco, Cottin, Vincent, McCarthy, Cormac. 2019. Pulmonary alveolar proteinosis. In Nature reviews. Disease primers, 5, 16. doi:10.1038/s41572-019-0066-3. https://pubmed.ncbi.nlm.nih.gov/30846703/

3. Zong, Fuliang, Li, Sha, Wang, Yifeng, Hu, Lingfei, Yang, Huiying. 2022. Csf2ra deletion attenuates acute lung injuries induced by intratracheal inoculation of aerosolized ricin in mice. In Frontiers in immunology, 13, 900755. doi:10.3389/fimmu.2022.900755. https://pubmed.ncbi.nlm.nih.gov/36203597/

4. Shima, Kenjiro, Arumugam, Paritha, Sallese, Anthony, Trapnell, Bruce C, Suzuki, Takuji. 2022. A murine model of hereditary pulmonary alveolar proteinosis caused by homozygous Csf2ra gene disruption. In American journal of physiology. Lung cellular and molecular physiology, 322, L438-L448. doi:10.1152/ajplung.00175.2021. https://pubmed.ncbi.nlm.nih.gov/35043685/