Made to order: emergency myelopoiesis and demand-adapted innate immune cell production

Abstract

Definitive haematopoiesis is the process by which haematopoietic stem cells, located in the bone marrow, generate all haematopoietic cell lineages in healthy adults. Although highly regulated to maintain a stable output of blood cells in health, the haematopoietic system is capable of extensive remodelling in response to external challenges, prioritizing the production of certain cell types at the expense of others. In this Review, we consider how acute insults, such as infections and cytotoxic drug-induced myeloablation, cause molecular, cellular and metabolic changes in haematopoietic stem and progenitor cells at multiple levels of the haematopoietic hierarchy to drive accelerated production of the mature myeloid cells needed to resolve the initiating insult. Moreover, we discuss how dysregulation or subversion of these emergency myelopoiesis mechanisms contributes to the progression of chronic inflammatory diseases and cancer. Acute infection and other insults cause extensive remodelling in the bone marrow to drive the production of new blood cells, often prioritizing the production of mature myeloid cells at the expense of other blood cell types. Here, the authors describe how haematopoiesis is affected by acute demand and how this can contribute to inflammatory disease and cancer when dysregulated.