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 IFN alpha 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.Plasmacytoid dendritic cells monitor the bone marrow for apoptotic megakaryocytes (MKs) and deliver IFN alpha to the MK niche, triggering local on-demand proliferation and maturation of MK progenitors.
Plasmacytoid dendritic cells control homeostasis of megakaryopoiesis / Gaertner, F; Ishikawa-Ankerhold, H; Stutte, S; Fu, Ww; Weitz, J; Dueck, A; Nelakuditi, B; Fumagalli, V; van den Heuvel, D; Belz, L; Sobirova, G; Zhang, Z; Titova, A; Navarro, Am; Pekayvaz, K; Lorenz, M; von Baumgarten, L; Kranich, J; Straub, T; Popper, B; Zheden, V; Kaufmann, Wa; Guo, Cl; Piontek, G; von Stillfried, S; Boor, P; Colonna, M; Clauss, S; Schulz, C; Brocker, T; Walzog, B; Scheiermann, C; Aird, Wc; Nerlov, C; Stark, K; Petzold, T; Engelhardt, S; Sixt, M; Hauschild, R; Rudelius, M; Oostendorp, Raj; Iannacone, M; Heinig, M; Massberg, S. - In: NATURE. - ISSN 0028-0836. - (2024). [10.1038/s41586-024-07671-y]
Plasmacytoid dendritic cells control homeostasis of megakaryopoiesis
Fumagalli, V
Membro del Collaboration Group
;Iannacone, M
Membro del Collaboration Group
;
2024-01-01
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 IFN alpha 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.Plasmacytoid dendritic cells monitor the bone marrow for apoptotic megakaryocytes (MKs) and deliver IFN alpha to the MK niche, triggering local on-demand proliferation and maturation of MK progenitors.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
