Feedback-loop regulation of granulopoiesis. Granulopoiesis is demand driven in the steady state and in case of emergency. The feedback loop contains HSCs proliferating and differentiating into the myeloid lineage (common myeloid progenitor/granulocyte-monocyte progenitor) at the expense of lymphoid cells. Bone marrow emigration, demargination, and extravasation are dependent on chemokine signaling and adhesion molecules. Engulfment of aged apoptotic neutrophils generates an anti-inflammatory signal. Phagocytes like MΦs and DCs thus generate a negative feedback on granulopoiesis. Disinhibition (lack of neutrophils, enhanced danger signaling) may lead to IL-23, IL-17, and G-CSF secretion. Hematopoiesis is regulated by niche-forming cells, with myeloid cytokines, chemokines, and size as determining factors. The microbiome-generating PAMPs, the inflammasome integrating danger signaling, and circadian rhythms symbolized by zeitgeber time are suggested to represent the central, sine qua non regulators. CAR, CXC ligand 12–abundant reticular cell; CLP, common lymphoid progenitor; CMP, common myeloid progenitor; GMP, granulocyte/macrophage progenitor; HSC, hematopoietic stem cell; ILC, innate lymphoid cell; LXR, liver X receptor; MPP, multipotent progenitor; MSC, mesenchymal stem cell; ZT, zeitgeber time.