This cytokine is a haematopoietic growth factor that drives the survival, proliferation and differentiation of granulocyte and macrophage progenitor cells, and functions as a terminal differentiation and activation signal for mature myeloid cells.
GM-CSF is produced by activated T cells, macrophages, endothelial cells, fibroblasts and mast cells rather than being constitutively expressed, positioning it as an inducible emergency haematopoiesis signal rather than a steady-state one. It promotes the differentiation of monocytes into dendritic cells and inflammatory macrophages, primes neutrophils and eosinophils, and is a standard component of media for the ex vivo generation of monocyte-derived dendritic cells and macrophages.
Signalling through the GM-CSF receptor upregulates transcriptional programmes governing (i) cell cycle entry and proliferation via STAT5 and cyclin D, (ii) survival via BCL-2 family members and PI3K/AKT, (iii) myeloid lineage commitment via PU.1 and IRF factors, and (iv) inflammatory effector function via NF-kB. The protein adopts a compact four-helix bundle fold of the short-chain class of the haematopoietin cytokine family, stabilised by two intrachain disulfide bonds.
