Csf2ra, 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 signaling pathway, which is involved in various biological processes such as cell survival, proliferation, and differentiation [1].

In African swine fever virus (ASFV) infection, ASFV CD2v interacts with CSF2RA to regulate the JAK2-STAT3 pathway, inhibit apoptosis, and facilitate virus replication. CSF2RA siRNA downregulates the JAK2-STAT3 pathway, promotes apoptosis, and inhibits ASFV replication [1]. In mice, Csf2ra knockout (KO) attenuates acute lung injuries induced by intratracheal inoculation of aerosolized ricin. The activity levels of pro-inflammatory pathways in Csf2ra KO mice are decreased, and neutrophil chemotaxis and recruitment are inhibited after ricin-exposure [2]. In a murine model of hereditary pulmonary alveolar proteinosis, homozygous Csf2ra gene ablation causes a disease similar to that in children with CSF2RA mutations, with functional defects in alveolar macrophages [3].

In conclusion, Csf2ra is essential for the activation of the JAK2-STAT3 pathway. Gene-knockout models of Csf2ra have revealed its role in viral replication, acute lung injury, and hereditary pulmonary alveolar proteinosis, providing insights into the underlying mechanisms of these diseases and potential therapeutic targets.

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. 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/

3. 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/