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Modulation of Myelopoiesis Progenitors Is an Integral Component of Trained Immunity
Open accessAbstract
Trained innate immunity fosters a sustained favorable response of myeloid cells to a secondary challenge, despite their short lifespan in circulation. We thus hypothesized that trained immunity acts via modulation of hematopoietic stem and progenitor cells (HSPCs). Administration of β-glucan (prototypical trained-immunity-inducing agonist) to mice induced expansion of progenitors of the myeloid lineage, which was associated with elevated signaling by innate immune mediators, such as IL-1β and granulocyte-macrophage colony-stimulating factor (GM-CSF), and with adaptations in glucose metabolism and cholesterol biosynthesis. The trained-immunity-related increase in myelopoiesis resulted in a beneficial response to secondary LPS challenge and protection from chemotherapy-induced myelosuppression in mice. Therefore, modulation of myeloid progenitors in the bone marrow is an integral component of trained immunity, which to date, was considered to involve functional changes of mature myeloid cells in the periphery.
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“Studies have shown that TII occurs not only in mature myeloid cells, as previously believed, but also in immature progenitors, and thus can be long-lived [74,76].”
From Clonal hematopoiesis and inflammation – the perpetual cycle (2023) · cites this paper as [76]
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Metadata
- Authors
- Mitroulis, I., Ruppova, K., Wang, B., Chen, L.-S., Grzybek, M., Grinenko, T., Eugster, A., Troullinaki, M., Palladini, A., Kourtzelis, I., Chatzigeorgiou, A., Schlitzer, A., Beyer, M., Joosten, L. A. B., Isermann, B., Lesche, M., Petzold, A., Simons, K., Henry, I., Dahl, A., Schultze, J. L., Wielockx, B., Zamboni, N., Mirtschink, P., Coskun, Ü., Hajishengallis, G., Netea, M. G., & Chavakis, T.
- Affiliations
- Technische Universität Dresden (DE)
- University of Pennsylvania (US)
- Center for Regenerative Therapies Dresden (DE)
- Helmholtz Munich (DE)
- University of Bonn (DE)
- Radboud University Nijmegen (NL)
- Otto-von-Guericke-Universität Magdeburg (DE)
- Biotechnologisches Zentrum (DE)
- Max Planck Institute of Molecular Cell Biology and Genetics (DE)
- ETH Zurich (CH)
- Corresponding author
- Mitroulis, Ioannis
- Chavakis, Triantafyllos
- ORCID
- Mitroulis, Ioannis
- Ruppova, Klara
- Wang, Baomei
- Chen, Lan-Sun
- Grinenko, Tatyana
- Eugster, Anne
- Palladini, Alessandra
- Kourtzelis, Ioannis
- Chatzigeorgiou, Antonios
- Schlitzer, Andreas
- Beyer, Marc
- Joosten, Leo A.B.
- Isermann, Berend
- Lesche, Mathias
- Simons, Kai
- Henry, Ian
- Dahl, Andreas
- Schultze, Joachim L.
- Wielockx, Ben
- Zamboni, Nicola
- Mirtschink, Peter
- Coskun, Ünal
- Hajishengallis, George
- Netea, Mihai G.
- Chavakis, Triantafyllos
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2018-01
- Volume
- 172
- Issue
- 1-2
- Pages
- 147-161.e12
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC5766828
- OpenAlex
- W2783037826
- Cited by
- 1,100
- References
- 67
- Citations by year
- 2026: 134 · 2025: 147 · 2024: 127 · 2023: 128 · 2022: 123 · 2021: 148 · 2020: 134 · 2019: 90 · 2018: 67
- FWCI
- 47.18
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- Site cant be reached (submittedVersion, cc-by-nc-nd)
- DZNE Pub (submittedVersion, other-oa)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion, cc-by-nc-nd)
- Radboud Repository (Radboud University) (submittedVersion)
- Repository for Publications and Research Data (ETH Zurich) (submittedVersion, cc-by-nc-nd)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- ETH Zürich Research Collection
- Funders
- ERC (DEMETINL, #310372)
- Deutsche Forschungsgemeinschaft (CH279/5-1, TR-SFB127, SFB 854/B26N)
- NIH (DE024716, DE026152)
- German Federal Ministry of Education and Research
- Netherlands Association for Scientific Research
- Netherlands Heart Foundation (CVON2012-03)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- trained immunity, myelopoiesis, hematopoietic stem and progenitor cells, β-glucan, innate immunity, IL-1β, GM-CSF, glucose metabolism, cholesterol biosynthesis, lipopolysaccharide challenge, chemotherapy-induced myelosuppression, bone marrow, myeloid lineage
- MeSH terms
- Animals, Cells, Cultured, Immunity, Innate, Immunologic Memory, Male, Mice, Inbred C57BL, Granulocyte-Macrophage Colony-Stimulating Factor, Myeloid Progenitor Cells, Myelopoiesis, beta-Glucans, Mice, Interleukin-1beta
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