Plasmacytoid dendritic cells control homeostasis of megakaryopoiesis
Gärtner FR, Ishikawa-Ankerhold H, Stutte S, Fu W, Weitz J, Dueck A, Nelakuditi B, Fumagalli V, Van Den Heuvel D, Belz L, Sobirova G, Zhang Z, Titova A, Navarro AM, Pekayvaz K, Lorenz M, Von Baumgarten L, Kranich J, Straub T, Popper B, Zheden V, Kaufmann W, Guo C, Piontek G, Von Stillfried S, Boor P, Colonna M, Clauß S, Schulz C, Brocker T, Walzog B, Scheiermann C, Aird WC, Nerlov C, Stark K, Petzold T, Engelhardt S, Sixt MK, Hauschild R, Rudelius M, Oostendorp RAJ, Iannacone M, Heinig M, Massberg S. 2024. Plasmacytoid dendritic cells control homeostasis of megakaryopoiesis. Nature. 631, 645–653.
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Author
Gaertner, FlorianISTA 
;
Ishikawa-Ankerhold, Hellen;
Stutte, Susanne;
Fu, Wenwen;
Weitz, Jutta;
Dueck, Anne;
Nelakuditi, Bhavishya;
Fumagalli, Valeria;
Van Den Heuvel, Dominic;
Belz, Larissa;
Sobirova, Gulnoza;
Zhang, Zhe
All
;
Ishikawa-Ankerhold, Hellen;
Stutte, Susanne;
Fu, Wenwen;
Weitz, Jutta;
Dueck, Anne;
Nelakuditi, Bhavishya;
Fumagalli, Valeria;
Van Den Heuvel, Dominic;
Belz, Larissa;
Sobirova, Gulnoza;
Zhang, Zhe
All
Abstract
Platelet homeostasis is essential for vascular integrity and immune defence1,2. Although the process of platelet formation by fragmenting megakaryocytes (MKs; thrombopoiesis) has been extensively studied, the cellular and molecular mechanisms required to constantly replenish the pool of MKs by their progenitor cells (megakaryopoiesis) remains unclear3,4. Here we use intravital imaging to track the cellular dynamics of megakaryopoiesis over days. We identify plasmacytoid dendritic cells (pDCs) as homeostatic sensors that monitor the bone marrow for apoptotic MKs and deliver IFNα to the MK niche triggering local on-demand proliferation and maturation of MK progenitors. This pDC-dependent feedback loop is crucial for MK and platelet homeostasis at steady state and under stress. pDCs are best known for their ability to function as vigilant detectors of viral infection5. We show that virus-induced activation of pDCs interferes with their function as homeostatic sensors of megakaryopoiesis. Consequently, activation of pDCs by SARS-CoV-2 leads to excessive megakaryopoiesis. Together, we identify a pDC-dependent homeostatic circuit that involves innate immune sensing and demand-adapted release of inflammatory mediators to maintain homeostasis of the megakaryocytic lineage.
Publishing Year
Date Published
2024-07-18
Journal Title
Nature
Acknowledgement
We thank S. Helmer, N. Blount, E. Raatz and Z. Sisic for technical assistance. This work was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) SFB 1123 (S.M. project B06); SFB 914 (S.M. projects B02 and Z01, H.I.-A. project Z01, S.S. project A06, K.S. project B02, C. Schulz project A10, B.W. project A02, C. Scheiermann project B09); SFB 1054 (T.B. project B03); FOR2033 (F.G., R.A.J.O., S.M.); Individual research grant project ID: 514478744 (F.G.); Heisenberg Programme project ID: 514477451 (F.G.); the DZHK (German Center for Cardiovascular Research) (MHA 1.4VD (S.M.), Postdoc Start-up Grant, 81×3600213 (F.G.)); and LMUexcellence NFF (F.G.). W.F. received funding from China Scholarship Council (CSC, no. 201306270012). P.B. is supported by the German Research Foundation (DFG, project IDs 322900939, 432698239 and 445703531), European Research Council (ERC Consolidator grant no. 101001791) and the Federal Ministry of Education and Research (BMBF, STOP-FSGS-01GM2202C and NATON within the framework of the Network of University Medicine, no. 01KX2121). S.v.S. is supported by the START-Program of the Faculty of Medicine of the RWTH Aachen University (AZ 125/17). A.D. and S.E. are supported by the German Research Foundation (SFB TRR 267); S.E. by the BMBF in the framework of the Cluster4future program (CNATM—Cluster for Nucleic Acid Therapeutics Munich). This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 833440 to S.M.). F.G. received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 747687. The project is funded by the European Union (ERC, MEKanics, 101078110). Views and opinions expressed are those of the author(s) only and do not necessarily reflect those of the European Union or the European Research Council Executive Agency. Neither the European Union nor the granting authority can be held responsible for them.
Volume
631
Page
645-653
ISSN
eISSN
IST-REx-ID
Cite this
Gärtner FR, Ishikawa-Ankerhold H, Stutte S, et al. Plasmacytoid dendritic cells control homeostasis of megakaryopoiesis. Nature. 2024;631:645-653. doi:10.1038/s41586-024-07671-y
Gärtner, F. R., Ishikawa-Ankerhold, H., Stutte, S., Fu, W., Weitz, J., Dueck, A., … Massberg, S. (2024). Plasmacytoid dendritic cells control homeostasis of megakaryopoiesis. Nature. Springer Nature. https://doi.org/10.1038/s41586-024-07671-y
Gärtner, Florian R, Hellen Ishikawa-Ankerhold, Susanne Stutte, Wenwen Fu, Jutta Weitz, Anne Dueck, Bhavishya Nelakuditi, et al. “Plasmacytoid Dendritic Cells Control Homeostasis of Megakaryopoiesis.” Nature. Springer Nature, 2024. https://doi.org/10.1038/s41586-024-07671-y.
F. R. Gärtner et al., “Plasmacytoid dendritic cells control homeostasis of megakaryopoiesis,” Nature, vol. 631. Springer Nature, pp. 645–653, 2024.
Gärtner FR, Ishikawa-Ankerhold H, Stutte S, Fu W, Weitz J, Dueck A, Nelakuditi B, Fumagalli V, Van Den Heuvel D, Belz L, Sobirova G, Zhang Z, Titova A, Navarro AM, Pekayvaz K, Lorenz M, Von Baumgarten L, Kranich J, Straub T, Popper B, Zheden V, Kaufmann W, Guo C, Piontek G, Von Stillfried S, Boor P, Colonna M, Clauß S, Schulz C, Brocker T, Walzog B, Scheiermann C, Aird WC, Nerlov C, Stark K, Petzold T, Engelhardt S, Sixt MK, Hauschild R, Rudelius M, Oostendorp RAJ, Iannacone M, Heinig M, Massberg S. 2024. Plasmacytoid dendritic cells control homeostasis of megakaryopoiesis. Nature. 631, 645–653.
Gärtner, Florian R., et al. “Plasmacytoid Dendritic Cells Control Homeostasis of Megakaryopoiesis.” Nature, vol. 631, Springer Nature, 2024, pp. 645–53, doi:10.1038/s41586-024-07671-y.
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