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  • Review Article
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Inflammatory modulation of HSCs: viewing the HSC as a foundation for the immune response

Key Points

  • Haematopoietic progenitors proliferate during infections, even in the absence of peripheral cytopenia.

  • Haematopoietic stem cells (HSCs) respond to both direct and indirect signals during infection.

  • Direct signalling to HSCs during infection may occur via pattern recognition receptors, such as Toll-like receptors.

  • Indirect signalling to HSCs during infection is mediated by pro-inflammatory cytokines, the most extensively characterized of which are the interferons.

  • Baseline interferon signalling and tight regulation of this signalling are imperative to maintain HSC and peripheral cell populations.

  • Cytokine-mediated activation of HSCs impairs their self-renewal capacity.

Abstract

Cells of the innate and adaptive immune systems are the progeny of a variety of haematopoietic precursors, the most primitive of which is the haematopoietic stem cell. Haematopoietic stem cells have been thought of generally as dormant cells that are only called upon to divide under extreme conditions, such as bone marrow ablation through radiation or chemotherapy. However, recent studies suggest that haematopoietic stem cells respond directly and immediately to infections and inflammatory signals. In this Review, we summarize the current literature regarding the effects of infection on haematopoietic stem cell function and how these effects may have a pivotal role in directing the immune response from the bone marrow.

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Figure 1: The haematopoietic tree.
Figure 2: The push and pull on HSCs.
Figure 3: Immunomodulation of HSCs during infection.
Figure 4: Inflammation as a rheostat for haematopoietic stem cell differentiation.

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Acknowledgements

We would like to thank M. Baldridge, G. Challen and F. Zohren for helpful discussions and critical reading of the manuscript. K.Y.K. is supported by the US National Heart, Lung, and Blood Institute (NHLBI), and M.A.G. is supported by the US National Institutes of Health, the US Department of Defense and the Samuel Waxman Cancer Research Foundation (New York, USA).

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Correspondence to Margaret A. Goodell.

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Glossary

Common myeloid progenitors

(CMPs). Progenitor cells that give rise to megakaryocyte and erythrocyte progenitors (MEPs) or granulocyte and macrophage progenitors (GMPs) and, subsequently, the mature progeny of those cells.

Lineage marker-negative SCA1+KIT+ cells

(LSK cells). A commonly used population of bone marrow cells that is enriched for haematopoietic stem cells but also contains a heterogeneous mix of multipotent progenitors and other committed progenitor cells.

Hoechst 33342

A lipophilic fluorescent stain for labelling DNA that is excited by ultraviolet light. Haematopoietic stem cells are capable of Hoechst 33342 efflux.

Common lymphoid progenitors

(CLPs). Progenitor cells that are committed to the lymphoid lineage that can give rise to all lymphocyte subsets, including B cells, T cells and natural killer cells.

Acquired aplastic anaemia

A syndrome of bone marrow hypocellularity combined with peripheral pancytopenia.

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King, K., Goodell, M. Inflammatory modulation of HSCs: viewing the HSC as a foundation for the immune response. Nat Rev Immunol 11, 685–692 (2011). https://doi.org/10.1038/nri3062

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