Granulocyte-macrophage colony-stimulating factor receptor signaling axis (GM-CSF/GM-CSFR axis)

The Granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling axis is a pivotal pathway in the regulation of the innate immune response and myeloid cell homeostasis (Source: Nature Reviews Rheumatology, 2020). It comprises the cytokine GM-CSF and its high-affinity receptor, a complex of GM-CSFRα (CD116) and the common beta subunit (βc, CD131) (Source: Blood, 2017). Binding of GM-CSF triggers the JAK2-STAT5 signaling cascade, promoting the survival, proliferation, and activation of macrophages, neutrophils, and dendritic cells (Source: Frontiers in Immunology, 2019). In pathological states, such as rheumatoid arthritis and COVID-19-induced cytokine storms, excessive GM-CSF signaling drives chronic inflammation and tissue damage (Source: Lancet Rheumatology, 2021). Conversely, the axis is essential for pulmonary surfactant clearance, and its disruption leads to pulmonary alveolar proteinosis (Source: NEJM, 2020). Therapeutic interventions include monoclonal antibodies that either neutralize the GM-CSF ligand or block the receptor alpha subunit to dampen hyper-inflammation (Source: Annals of the Rheumatic Diseases, 2019). Additionally, recombinant GM-CSF is utilized as an agonist to stimulate white blood cell production in patients with neutropenia (Source: StatPearls, 2023).

Other names

CSF2/CSF2R axisColony-stimulating factor 2 receptor signalingGM-CSF signaling pathwayCD116/CD131 signaling axis

Neutralization of the GM-CSF ligand or competitive inhibition of the GM-CSFR alpha subunit to prevent downstream JAK2/STAT5 signaling and myeloid cell activation (Source: Nature Reviews Rheumatology, 2020).