德国慕尼黑大学医院Florian Gaertner等共同合作，近期取得重要工作进展。他们研究提出，浆细胞样树突状细胞控制巨核细胞生成的稳态。相关研究成果2024年7月10日在线发表于《自然》杂志上。

据介绍，血小板稳态对血管完整性和免疫防御至关重要。尽管对巨核细胞（MK；血栓形成）碎裂形成血小板的过程进行了广泛研究，但其祖细胞（巨核细胞生成）不断补充巨核细胞池所需的细胞和分子机制仍不清楚。

研究人员使用活体成像来跟踪几天内巨核细胞生成的动力学。研究人员将浆细胞样树突状细胞（pDC）鉴定为稳态传感器，可监测骨髓中凋亡的MK，并将IFNα递送到MK生态位，从而触发MK祖细胞的局部按需增殖和成熟。这种依赖于pDC的反馈回路在稳态和压力下对MK和血小板稳态至关重要。pDC最为人所知的是它们能够作为病毒感染的探测器。研究人员发现，病毒诱导的pDC激活干扰了它们作为巨核生成稳态传感器的功能。因此，严重急性呼吸系统综合征冠状病毒2型（SARS-CoV-2）激活pDC会导致巨核细胞过度生成。

总之，研究人员共同确定了一个依赖于pDC的稳态回路，该回路涉及先天免疫感应和炎症介质的需求适应释放，以维持巨核细胞谱系的稳态。

附：英文原文

Title: Plasmacytoid dendritic cells control homeostasis of megakaryopoiesis

Author: Gaertner, Florian, Ishikawa-Ankerhold, Hellen, Stutte, Susanne, Fu, Wenwen, Weitz, Jutta, Dueck, Anne, Nelakuditi, Bhavishya, Fumagalli, Valeria, van den Heuvel, Dominic, Belz, Larissa, Sobirova, Gulnoza, Zhang, Zhe, Titova, Anna, Navarro, Alejandro Martinez, Pekayvaz, Kami, Lorenz, Michael, von Baumgarten, Louisa, Kranich, Jan, Straub, Tobias, Popper, Bastian, Zheden, Vanessa, Kaufmann, Walter Anton, Guo, Chenglong, Piontek, Guido, von Stillfried, Saskia, Boor, Peter, Colonna, Marco, Clau, Sebastian, Schulz, Christian, Brocker, Thomas, Walzog, Barbara, Scheiermann, Christoph, Aird, William C., Nerlov, Claus, Stark, Konstantin, Petzold, Tobias, Engelhardt, Stefan, Sixt, Michael, Hauschild, Robert, Rudelius, Martina, Oostendorp, Robert A. J., Iannacone, Matteo, Heinig, Matthias, Massberg, Steffen

Issue&Volume: 2024-07-10

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.

DOI: 10.1038/s41586-024-07671-y

Source: https://www.nature.com/articles/s41586-024-07671-y