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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.

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Fig. 1: Haematopoiesis is a process of continuous differentiation.
Fig. 2: Stress haematopoiesis uses bypass mechanisms and independent trajectories for lineage amplification.
Fig. 3: Emergency myelopoiesis mechanisms remodel the haematopoietic system to meet demand.
Fig. 4: Emergency myelopoiesis mechanisms are regulated by the bone marrow niche.
Fig. 5: Emergency myelopoiesis responses are specific to different infectious pathogens.
Fig. 6: Chronic inflammatory diseases dysregulate emergency myelopoiesis responses to accelerate disease.
Fig. 7: Solid cancers subvert emergency myelopoiesis mechanisms to promote tumour growth and metastasis.

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Acknowledgements

J.W.S. discloses support for this work from William Raveis Charitable Fund Fellowship of the Damon Runyon Cancer Research Foundation DRG-2493-23 and EMBO fellowship ALTF-196-2021. O.C.O. acknowledges support from CRI/Margaret Damman Eisner postdoctoral fellowship CRI3617. E.P. acknowledges support from NIH R01CA184014 and NIH R35HL135763. The funders had no role in the preparation of this manuscript.

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Swann, J.W., Olson, O.C. & Passegué, E. Made to order: emergency myelopoiesis and demand-adapted innate immune cell production. Nat Rev Immunol 24, 596–613 (2024). https://doi.org/10.1038/s41577-024-00998-7

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