ORCID: https://orcid.org/0000-0001-6120-3723; Ishikawa-Ankerhold, Hellen ORCID: https://orcid.org/0000-0003-0307-7022; Stutte, Susanne; Fu, Wenwen; Weitz, Jutta; Dueck, Anne ORCID: https://orcid.org/0000-0002-7956-6327; Nelakuditi, Bhavishya; Fumagalli, Valeria ORCID: https://orcid.org/0000-0003-2583-2498; van den Heuvel, Dominic ORCID: https://orcid.org/0000-0002-8998-0396; Belz, Larissa; Sobirova, Gulnoza; Zhang, Zhe; Titova, Anna; Navarro, Alejandro Martinez ORCID: https://orcid.org/0000-0003-3893-1719; Pekayvaz, Kami; Lorenz, Michael; von Baumgarten, Louisa ORCID: https://orcid.org/0000-0002-6634-0927; Kranich, Jan ORCID: https://orcid.org/0000-0002-9928-4132; Straub, Tobias ORCID: https://orcid.org/0000-0002-0547-0453; Popper, Bastian; Zheden, Vanessa ORCID: https://orcid.org/0000-0002-9438-4783; Kaufmann, Walter Anton; Guo, Chenglong; Piontek, Guido; Stillfried, Saskia von ORCID: https://orcid.org/0000-0002-5260-8494; Boor, Peter ORCID: https://orcid.org/0000-0001-9921-4284; Colonna, Marco ORCID: https://orcid.org/0000-0001-5222-4987; Clauß, Sebastian ORCID: https://orcid.org/0000-0002-5675-6128; Schulz, Christian ORCID: https://orcid.org/0000-0002-8149-0747; Brocker, Thomas ORCID: https://orcid.org/0000-0001-7060-5433; Walzog, Barbara ORCID: https://orcid.org/0000-0001-7729-6565; Scheiermann, Christoph ORCID: https://orcid.org/0000-0002-9212-0995; Aird, William C.; Nerlov, Claus ORCID: https://orcid.org/0000-0002-0544-735X; Stark, Konstantin ORCID: https://orcid.org/0000-0002-5369-8399; Petzold, Tobias; Engelhardt, Stefan ORCID: https://orcid.org/0000-0001-5378-8661; Sixt, Michael; Hauschild, Robert ORCID: https://orcid.org/0000-0001-9843-3522; Rudelius, Martina; Oostendorp, Robert A. J. ORCID: https://orcid.org/0000-0002-4947-0412; Iannacone, Matteo ORCID: https://orcid.org/0000-0002-9370-2671; Heinig, Matthias ORCID: https://orcid.org/0000-0002-5612-1720 und Massberg, Steffen ORCID: https://orcid.org/0000-0001-7387-3986
(2024):
Plasmacytoid dendritic cells control homeostasis of megakaryopoiesis.
In: Nature, Vol. 631, No. 8021: pp. 645-653
[PDF, 15MB]
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.
| Item Type: | Journal article |
|---|---|
| EU Funded Grant Agreement Number: | 833440 |
| EU Projects: | Horizon 2020 > ERC Grants > ERC Advanced Grant > ERC Grant 833440: IMMUNOTHROMBOSIS - Cross-talk between platelets and immunity - implications for host homeostasis and defense |
| Faculties: | Medicine > Medical Center of the University of Munich > Medical Clinic and Outpatient Clinic I (Cardiology) |
| Subjects: | 600 Technology > 610 Medicine and health |
| URN: | urn:nbn:de:bvb:19-epub-121884-8 |
| ISSN: | 0028-0836 |
| Language: | English |
| Item ID: | 121884 |
| Date Deposited: | 16. Oct 2024 10:41 |
| Last Modified: | 16. Oct 2024 10:41 |
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