免疫細胞が骨髄で血小板の成熟をモニター(Immune cells monitor blood platelet maturation in bone marrow)

2024-07-17 ミュンヘン大学(LMU)

<関連情報>

• https://www.lmu.de/en/newsroom/news-overview/news/immune-cells-monitor-blood-platelet-maturation-in-bone-marrow.html
• https://www.nature.com/articles/s41586-024-07671-y

形質細胞様樹状細胞が巨核球形成の恒常性を制御する Plasmacytoid dendritic cells control homeostasis of megakaryopoiesis

Florian Gaertner,Hellen Ishikawa-Ankerhold,Susanne Stutte,Wenwen Fu,Jutta Weitz,Anne Dueck,Bhavishya Nelakuditi,Valeria Fumagalli,Dominic van den Heuvel,Larissa Belz,Gulnoza Sobirova,Zhe Zhang,Anna Titova,Alejandro Martinez Navarro,Kami Pekayvaz,Michael Lorenz,Louisa von Baumgarten,Jan Kranich,Tobias Straub,Bastian Popper,Vanessa Zheden,Walter Anton Kaufmann,Chenglong Guo,Guido Piontek,… Steffen Massberg
Nature  Published:10 July 2024
DOI:https://doi.org/10.1038/s41586-024-07671-y

Abstract

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 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.