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CME Evaluation

Oral Communication Session

Platelets and Megakaryocytes

Session: Mega-insights

OC 18.4 - Plasmacytoid dendritic cells regulate tissue homeostasis of megakaryocytes

Sunday, June 23, 2024
10:15 – 10:30 ICT
Room: 211 A-D

    Presenting Author(s)

  • Florian Gaertner, MD, PhD

    Professor
    LMU Klinikum
    Munich, Bayern, Germany

    • Co-Author(s)

  • HI

    Hellen Ishikawa-Ankerhold

    PhD
    Department of Medicine I, LMU University Hospital, LMU Munich
    Munich, Bayern, Germany

  • SS

    Susanne Stutte

    PhD
    Institute of Cardiovascular Physiology and Pathophysiology, Biomedical Center, LMU Munich, Planegg-Martinsried, Germany
    Munich, Bayern, Germany

  • WF

    Wenwen Fu

    MD, PhD
    Department of Medicine I, University Hospital, LMU Munich
    Munich, Bayern, Germany

  • JW

    Jutta Weitz

    MD candidate
    Department of Medicine I, University Hospital, LMU Munich
    Munich, Bayern, Germany

  • AD

    Anne Dueck

    PhD
    Institut für Pharmakologie und Toxikologie, Technische Universität München (TUM), Munich, Germany
    Munich, Bayern, Germany

  • BN

    Bhavishya Nelakuditi

    PhD candidate
    Department of Medicine I, University Hospital, LMU Munich
    Munich, Bayern, Germany

  • VF

    Valeria Fumagalli

    PhD
    Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute and Vita-Salute San Raffaele University
    Milan, Lombardia, Italy

  • KP

    Kami Pekayvaz

    MD
    Department of Medicine I, University Hospital, LMU Munich
    Munnich, Bayern, Germany

  • ZZ

    Zhe Zhang

    PhD
    Department of Medicine I, University Hospital, LMU Munich
    Munich, Bayern, Germany

  • AM

    Alejandro Martinez Navarro

    PhD candidate
    Department of Medicine I, University Hospital, LMU Munich
    Munich, Bayern, Germany

  • KS

    Konstantin Stark

    MD
    Department of Medicine I, University Hospital, LMU Munich
    Munich, Bayern, Germany

  • SE

    Stefan Engelhardt

    MD, PhD
    Institut für Pharmakologie und Toxikologie, Technische Universität München (TUM), Munich, Germany
    Munich, Bayern, Germany

  • RH

    Robert Hauschild

    PhD
    Institute of Science and Technology Austria (ISTA)
    Klosterneuburg, Niederosterreich, Austria

  • MR

    Martina Rudelius

    MD
    Institute of Pathology, Ludwig-Maximilians-University Munich
    Munich, Bayern, Germany

  • Sv

    Saskia von Stillfried

    MD
    Institute of Pathology, RWTH Aachen University Hospital
    Munich, Bayern, Germany

  • PB

    Peter Boor

    MD, PhD
    Institute of Pathology, RWTH Aachen University Hospital
    Aachen, Nordrhein-Westfalen, Germany

  • MI

    Matteo Iannacone

    MD, PhD
    Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute and Vita-Salute San Raffaele University
    Milan, Lombardia, Italy

  • MH

    Matthias Heinig

    PhD
    Institute of Computational Biology, Deutsches Forschungszentrum für Gesundheit und Umwelt, Helmholtz Zentrum München and Department of Informatics, Technical University of Munich
    Munich, Bayern, Germany

  • Steffen Massberg

    MD
    Department of Medicine I, LMU University Hospital, LMU Munich
    Munich, Bayern, Germany

Background: Platelets are anucleate cell fragments that circulate in the blood to maintain vascular barrier function in health and disease. They are produced in the bone marrow by their precursors, the megakaryocytes. In a process called thrombopoiesis, megakaryocytes release platelets as their cell body is completely consumed. Consequently, replenishment of fragmented megakaryocytes from megakaryocyte progenitors (megakaryopoiesis) is required to ensure megakaryocyte homeostasis and sustained platelet production. The cellular and molecular mechanisms required to continuously replenish the pool of megakaryocytes from their progenitors remain unclear.

Aims: Here we aim to monitor the cellular dynamics of megakaryopoiesis and to identify the mechanisms underlying tissue homeostasis of megakaryocytes in the bone marrow niche.

Methods: We have developed an intravital imaging approach that allowed us to visualise megakaryopoiesis in the bone marrow over days using 2-photon microscopy. By using knockout mouse models, we characterised the role of immune cell populations in the regulation of megakaryopoiesis in the bone marrow niche and identified the underlying mechanism both in vitro (e.g. co-culture experiments) and in vivo (e.g. scRNAseq, whole-mount histology). In addition, bone marrow biopsies from patients were analysed to assess the clinical relevance of our findings.

Results: We have identified plasmacytoid dendritic cells (pDCs) as a leukocyte population in the bone marrow that plays a crucial role in megakaryopoiesis. pDCs act as homeostatic sensors that monitor the bone marrow for apoptotic megakaryocytes and release IFN-alpha to the megakaryocytic bone marrow niche, triggering proliferation and maturation of megakaryocytic progenitor cells. This fine-tuned coordination between platelet production and megakaryopoiesis is crucial for megakaryocyte and platelet homeostasis in steady state and under stress.

Conclusion(s): In conclusion, we have discovered a pDC-dependent homeostatic circuit that involves innate immune sensing and demand-driven release of inflammatory mediators to maintain tissue homeostasis of the megakaryocytic lineage.