PuSH - Publikationsserver des Helmholtz Zentrums München

Gaertner, F.* ; 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, A.M.* ; Pekayvaz, K.* ; Lorenz, M.* ; von Baumgarten, L.* ; Kranich, J.* ; Straub, T.* ; Popper, B.* ; Zheden, V.* ; Kaufmann, W.A.* ; Guo, C.* ; Piontek, G.* ; von Stillfried, S.* ; Boor, P.* ; Colonna, M.* ; Clauß, S.* ; Schulz, C.* ; Brocker, T.* ; Walzog, B.* ; Scheiermann, C.* ; Aird, W.C.* ; Nerlov, C.* ; Stark, K.* ; Petzold, T.* ; Engelhardt, S.* ; Sixt, M.* ; Hauschild, R.* ; Rudelius, M.* ; Oostendorp, R.A.J.* ; Iannacone, M.* ; Heinig, M. ; Massberg, S.*

Plasmacytoid dendritic cells control homeostasis of megakaryopoiesis.

Nature 631, 645-653 (2024)
Verlagsversion DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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.
Altmetric
Weitere Metriken?
[➜Einloggen]
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Hematopoietic Stem-cells; Megakaryocytes; Platelets; Macrophages; Infection; Bone; Thrombocytopenia; Immunity; Distinct; Mice
ISSN (print) / ISBN 0028-0836
e-ISSN 1476-4687
Zeitschrift Nature
Quellenangaben Band: 631, Heft: 8021, Seiten: 645-653 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Computational Biology (ICB)
Förderungen European Research Council (ERC)
German Research Foundation (DFG)
China Scholarship Council (CSC)
LM Uexcellence NFF
DZHK (German Center for Cardiovascular Research)
European Union (ERC)
European Union
BMBF
German Research Foundation
START-Program of the Faculty of Medicine of the RWTH Aachen University
Network of University Medicine
NATON
Federal Ministry of Education and Research (BMBF)
Deutsche Forschungsgemeinschaft (DFG, German Research foundation)