The pleiotropic effects of the GM-CSF rheostat on myeloid cell differentiation and function: more than a numbers game
- Journal Title
- Frontiers in Immunology
- Publication Type
- Journal Article
- Abstract
- Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) is a myelopoietic growth factor that has pleiotropic effects not only in promoting the differentiation of immature precursors into polymorphonuclear neutrophils (PMNs), monocytes/macrophages (MOs) and dendritic cells (DCs), but also in controlling the function of fully mature myeloid cells. This broad spectrum of GM-CSF action may elicit paradoxical outcomes-both immunostimulation and immunosuppression-in infection, inflammation, and cancer. The complexity of GM-CSF action remains to be fully unraveled. Several aspects of GM-CSF action could contribute to its diverse biological consequences. Firstly, GM-CSF as a single cytokine affects development of most myeloid cells from progenitors to mature immune cells. Secondly, GM-CSF activates JAK2/STAT5 and also activate multiple signaling modules and transcriptional factors that direct different biological processes. Thirdly, GM-CSF can be produced by different cell types including tumor cells in response to different environmental cues; thus, GM-CSF quantity can vary greatly under different pathophysiological settings. Finally, GM-CSF signaling is also fine-tuned by other less defined feedback mechanisms. In this review, we will discuss the role of GM-CSF in orchestrating the differentiation, survival, and proliferation during the generation of multiple lineages of myeloid cells (PMNs, MOs, and DCs). We will also discuss the role of GM-CSF in regulating the function of DCs and the functional polarization of MOs. We highlight how the dose of GM-CSF and corresponding signal strength acts as a rheostat to fine-tune cell fate, and thus the way GM-CSF may best be targeted for immuno-intervention in infection, inflammation and cancer.
- Publisher
- Frontiers Media
- Research Division(s)
- Immunology
- PubMed ID
- 31803190
- Publisher's Version
- https://doi.org/10.3389/fimmu.2019.02679
- Open Access at Publisher's Site
https://doi.org/10.3389/fimmu.2019.02679- NHMRC Grants
- NHMRC/1037321, NHMRC/1105209, NHMRC/1143976, NHMRC/1150425, NHMRC/1080321,
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- Refer to copyright notice on published article.
Creation Date: 2019-12-16 02:49:03
Last Modified: 2019-12-16 03:08:35