The Pleiotropic Effects of the GM-CSF Rheostat on Myeloid Cell Differentiation and Function: More Than a Numbers Game.

摘要: 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 controlling function fully mature myeloid cells. This broad spectrum GM-CSF action may elicit paradoxical outcomes-both immunostimulation immunosuppression-in infection, inflammation, cancer. The complexity remains to be unraveled. Several aspects could contribute its diverse biological consequences. Firstly, as single cytokine affects development most from progenitors immune Secondly, activates JAK2/STAT5 activate multiple signaling modules transcriptional factors direct different processes. Thirdly, can produced by cell types including tumor response environmental cues; thus, quantity vary greatly under pathophysiological settings. Finally, fine-tuned other less defined feedback mechanisms. In this review, we will discuss role orchestrating differentiation, survival, proliferation during generation lineages (PMNs, MOs, DCs). We regulating DCs functional polarization MOs. highlight how dose corresponding signal strength acts rheostat fine-tune fate, thus way best targeted for immuno-intervention inflammation