Csf2ra, encoding the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor alpha subunit, is a key receptor protein in the hematopoietic receptor superfamily, especially in myeloid cells. It activates receptor-associated JAK and STAT proteins, playing a crucial role in the JAK2-STAT3 pathway, which is involved in various biological processes such as cell survival, proliferation, and differentiation [1].

In an African swine fever virus (ASFV) infection study, CSF2RA was found to interact with the ASFV envelope glycoprotein CD2v. CSF2RA small interfering RNA (siRNA) downregulated the JAK2-STAT3 pathway, promoted apoptosis, and inhibited ASFV replication, indicating that ASFV uses the interaction between CD2v and CSF2RA to regulate the JAK2-STAT3 pathway and inhibit apoptosis for its own replication [1].

In mice, Csf2ra knockout (KO) led to attenuation of acute lung injuries induced by intratracheal inoculation of aerosolized ricin. Bioinformatics analysis showed that the activity levels of pro-inflammatory pathways, like the TNF and NF-κB signaling pathways, were decreased in Csf2ra KO mice, and neutrophil chemotaxis and recruitment were inhibited [2].

A murine model of hereditary pulmonary alveolar proteinosis (hPAP) was created by disrupting the Csf2ra gene. Macrophages from Csf2ra-/-mice had functional defects in phagocytosis, cholesterol clearance, and surfactant clearance, and the mice developed a progressive lung disease similar to hPAP in children caused by CSF2RA mutations [3].

In conclusion, Csf2ra is essential for normal function in multiple biological processes. Its role in regulating the JAK2-STAT3 pathway and influencing immune-related processes is significant. Gene-knockout mouse models of Csf2ra have provided valuable insights into diseases such as ASFV-induced infections, acute lung injuries, and hPAP, helping to understand the underlying molecular mechanisms and potentially paving the way for new therapeutic strategies.