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Publication : Plasmacytoid dendritic cells control homeostasis of megakaryopoiesis.

First Author	Gaertner F	Year	2024
Journal	Nature	Volume	631
Issue	8021	Pages	645-653
PubMed ID	38987596	Mgi Jnum	J:359160
Mgi Id	MGI:7707528	Doi	10.1038/s41586-024-07671-y
Citation	Gaertner F, et al. (2024) Plasmacytoid dendritic cells control homeostasis of megakaryopoiesis. Nature 631(8021):645-653

abstractText

Platelet homeostasis is essential for vascular integrity and immune defence(1,2). 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 unclear(3,4). 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 IFNalpha 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 infection(5). 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.

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