Open Access
REVIEW
GM-CSF: from emergency myelopoiesis to central innate immune memory
Paula Guerrero, M. Luisa Gil, Alberto Yáñez*
Instituto de Biotecnología y Biomedicina (BIOTECMED) and Departamento de Microbiología y Ecología, Facultad de Ciencias Biológicas, Universitat de València, Burjassot, Spain
* Corresponding Author: Alberto Yáñez. Email: 
European Cytokine Network https://doi.org/10.32604/ecn.2026.086544
Received 01 June 2026; Accepted 31 August 2026; Published online 18 September 2026
Abstract
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic cytokine classically recognized as a central regulator of emergency myelopoiesis, promoting the expansion and differentiation of hematopoietic stem and progenitor cells (HSPCs) towards the myeloid lineage during infection and inflammation. In addition, GM-CSF enhances myeloid cell recruitment and activation, boosting antimicrobial functions and inflammatory responses. This coordinated capacity to enhance myelopoiesis while amplifying effector functions reflects a broader property of GM-CSF to functionally reprogram the hematopoietic system, not only increasing myeloid output but also shaping the inflammatory potential of downstream myeloid cells. However, this enhanced potential must be tightly regulated to avoid tissue damage and the development of chronic inflammatory or autoimmune disorders driven by GM-CSF-activated cells. In this review, we integrate current knowledge of GM-CSF biology with emerging evidence supporting its role in shaping central innate immune memory. We highlight its capacity to induce divergent memory programs, promoting either trained immunity or tolerance depending on GM-CSF receptor (GM-CSFR) expression levels and downstream signaling strength across distinct stages of myelopoiesis. Finally, we discuss the relevance of these properties in different contexts and their current and potential therapeutic implications.
Keywords
GM-CSF; hematopoietic stem and progenitor cells; emergency myelopoiesis; innate immune memory
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