Neutrophil Functions in Periodontal Homeostasis

Figure 2

Neutrophil trafficking. A neutrophil rheostat (neutrostat) that maintains steady-state neutrophil levels involves the axis interleukin- (IL-) 23/IL-17/granulocyte colony-stimulating factor (G-CSF). Granulopoiesis takes place in the bone marrow where proliferation of granulocytic precursors is induced by G-CSF. The exit of mature neutrophils from the bone marrow into the blood circulation is also regulated by G-CSF. Circulating neutrophils roll on endothelial cells at sites of infection of inflammation. Upon firm adhesion mediated by integrins, neutrophils can transmigrate into the tissues. There, neutrophils perform their antimicrobial functions and then die by apoptosis. Apoptotic neutrophils are phagocytosed by macrophages. This initiates an anti-inflammatory signal that reduces IL-23 production from macrophages (black cross). IL-23 can activate Th17 lymphocytes to produce IL-17, which promotes granulopoiesis and neutrophil release by upregulation of G-CSF in fibroblasts. An interesting positive loop for neutrophil recruitment is found at chronic inflammation sites, where neutrophils can attract Th17 cells via CCL2 and CCL20 chemokines. In turn, Th17 cells recruit more neutrophils via CXC chemokines by inducing neutrophils to produce IL-17. Senescent neutrophils return to the bone marrow for clearance after they increase expression of CXCR4. Red arrows represent release of cytokines and chemokines from cells, and effect of these mediators on cells. Blue arrows represent movement of cells.