Regulation of stress-induced hematopoiesis

Abstract

Purpose of review: Hematopoietic stem cells can self-renew and also give rise to the entire repertoire of hematopoietic cells. During acute infectious and inflammatory stresses, the hematopoietic system can quickly adapt to demand by increasing output of innate immune cells many-fold, often at the expense of lymphopoiesis and erythropoiesis. We review recent advances in understanding the regulation of stress-induced hematopoiesis with a specific focus on the direct effects of inflammatory signaling on hematopoietic stem and progenitor cells (HSPCs).

Recent findings: Recent studies have highlighted several areas of exciting new developments in the field, including the complex interaction and crosstalk within HSPCs and between bone marrow mesenchymal stem cells and endothelial cells needed to achieve regulated myelopoiesis, identification of increased number of inflammatory and infectious molecules with direct effects on HSPCs, the critical role of inflammatory signaling on embryonic specification of hematopoietic stem cells, and the ability of cytokines to instruct lineage choice at the HSPC level.

Summary: These exciting new findings will shape our fundamental understanding of how inflammatory signaling regulates hematopoiesis in health and disease, and facilitate the development of potential interventions to treat hematologic diseases associated with altered inflammatory signaling.

Figure 1

Emerging concepts in the regulation of hematopoiesis by inflammatory signaling. A. Complex paracrine and autocrine signaling within HSPCs and between bone marrow stromal cells. IL-6 is produced by ST-HSCs and MPPs upon LPS stimulation and by MSCs upon IFNγ stimulation; G-CSF is produced by endothelial cells upon LPS stimulation; IL-6, IFNγ and G-CSF stimulate myelopoiesis via paracrine and/or autocrine signaling. B. An expanding list of PAMPs, DAMPs and cytokines with direct effects on HSPCs. C. Cytokines such as M-CSF and EPO can instruct lineage choice of uncommitted HSPCs by promoting lineage-specific transcriptional factor while suppressing the alternative cell fates. D. Inflammatory molecules, including TLR agonists, TNFα, IFNα and IFNγ, promote embryonic HSC cell fate specification from hemogenic endothelium through NF-κB, Stat3 and Notch pathway.