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Hematopoietic progenitor cells as integrative hubs for adaptation to and fine-tuning of inflammation

Nature Immunology volume 20, pages 802–811 (2019)Cite this article

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Abstract

Recent advances have highlighted the ability of hematopoietic stem and progenitor cells in the bone marrow to sense peripheral inflammation or infection and adapt through increased proliferation and skewing toward the myeloid lineage. Such adaptations can meet the increased demand for innate immune cells and can be beneficial in response to infection or myeloablation. However, the inflammation-induced adaptation of hematopoietic and myeloid progenitor cells toward enhanced myelopoiesis might also perpetuate inflammation in chronic inflammatory or cardio-metabolic diseases by generating a feed-forward loop between inflammation-adapted hematopoietic progenitor cells and the inflammatory disorder. Sustained adaptive responses of progenitor cells in the bone marrow can also contribute to trained immunity, a non-specific memory of earlier encounters that in turn facilitates the heightened response of these cells, as well as that of their progeny, to future challenges. Here we discuss the mechanisms that govern the adaptation of hematopoietic progenitor cells to inflammation and its sequelae in the pathogenesis of human disease.

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Fig. 1: Inflammatory adaptation of hematopoietic progenitor cells.
Fig. 2: Regulation of HSCs by their progeny in the BM niche.
Fig. 3: Adaptation of hematopoietic progenitor cells in cardio-metabolic disease.
Fig. 4: A detrimental feed-forward loop that links the adaptation of HSPCs to inflammation with chronic inflammatory disease.

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Acknowledgements

Supported by the US National Institutes of Health (DE015254, DE024153 and DE024716 to G.H. and DE026152 to G.H. and T.C.), the European Research Council (DEMETINL-683145 to T.C.), the Deutsche Forschungsgemeinschaft (SFB/TRR 205 to T.C.) and the National Center for Tumor Diseases, Partner Site Dresden (I.M.).

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  1. These authors contributed equally: Triantafyllos Chavakis, Ioannis Mitroulis and George Hajishengallis.

Authors and Affiliations

  1. Institute for Clinical Chemistry and Laboratory Medicine, University Hospital and Faculty of Medicine Carl Gustav Carus of TU Dresden, Dresden, Germany

    Triantafyllos Chavakis & Ioannis Mitroulis

  2. National Center for Tumor Diseases, Partner Site Dresden, of the German Cancer Research Center, Heidelberg and of the Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, and of the Helmholtz Association/Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany

    Ioannis Mitroulis

  3. Department of Haematology and Laboratory of Molecular Hematology, Democritus University of Thrace, Alexandroupolis, Greece

    Ioannis Mitroulis

  4. University of Pennsylvania, Penn Dental Medicine, Department of Microbiology, Philadelphia, PA, USA

    George Hajishengallis

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Chavakis, T., Mitroulis, I. & Hajishengallis, G. Hematopoietic progenitor cells as integrative hubs for adaptation to and fine-tuning of inflammation. Nat Immunol 20, 802–811 (2019). https://doi.org/10.1038/s41590-019-0402-5

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