Figure 2 GM-CSF — a key player in inflammation and autoimmunity

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Figure 2 GM-CSF — a key player in inflammation and autoimmunity Figure 2 | GM-CSF — a key player in inflammation and autoimmunity. (1) Granulocyte-macrophage colony stimulating factor (GM-CSF) stimulates haematopoietic progenitor cells in the bone marrow to generate differentiated myeloid-cell progeny (neutrophils, eosinophils and monocyte/macrophages). (2) GM-CSF enhances trafficking of myeloid cells through activated endothelium of blood vessels, and can also contribute to monocyte and macrophage accumulation in blood vessels during atherosclerosis. (3) GM-CSF promotes activation, differentiation, survival and proliferation of trafficking monocytes and macrophages as well as resident tissue macrophages in inflamed tissues such as the synovial joint in rheumatoid arthritis (RA). Activated M1 macrophages produce cytokines, including GM-CSF and other proinflammatory cytokines such as TNF, IL-6 and IL-1, lipid-derived mediators and chemokines. These mediators promote the recruitment of inflammatory cells and the activation of resident fibroblast-like synoviocytes (FLSs). Local GM-CSF production leads to activation of the vasculature and bone marrow and promotes the differentiation of effector T cells at inflamed sites and draining lymph nodes. GM-CSF also has a homeostatic local role in normal tissue macrophage and dendritic-cell survival and/or function, at least in the lung and in the gut. (4) GM-CSF regulates the phenotype of antigen-presenting cells in inflamed tissues and draining lymph nodes by promoting the differentiation of infiltrating monocytes into M1 macrophages and, possibly, monocyte-derived dendritic cells (MoDCs). (5) The production of IL-23 by macrophages and MoDCs, in combination with other cytokines such as IL-6 and IL-1, modulates T-cell differentiation. (6) Locally produced GM-CSF acts on sensory neurons expressing the GM-CSF receptor, transmitting painful stimuli to ascending nociceptive pathways in the spinal cord and brain. Wicks, I. P. & Roberts, A. W. (2015) Targeting GM‑CSF in inflammatory diseases Nat. Rev. Rheumatol. doi:10.1038/nrrheum.2015.161