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Nature:Emfret授权代理现货血小板清除抗体助力血小板稳态研究

更新时间:2024-08-17   点击次数:364次

中文摘要:

血小板稳态对于血管完整性和免疫防御至关重要。尽管通过分裂巨核细胞(MKs;血小板生成)形成血小板的过程已得到广泛研究,但其祖细胞(巨核细胞生成)不断补充MKs库所需的细胞和分子机制仍不清楚。在这里,我们使用活体成像来追踪巨核生成细胞在几天内的动态。我们将浆细胞样树突状细胞 (pDC) 确定为稳态传感器,可监测骨髓中的凋亡 MK 并将 IFNα 输送到 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 的反馈回路对于稳态和压力下的 MK 和血小板稳态至关重要。pDC 最出名的是它们能够作为病毒感染的警戒检测器5。我们发现,病毒诱导的 pDC 激活会干扰它们作为巨核生成稳态传感器的功能。因此,SARS-CoV-2 激活 pDC 会导致过度的巨核生成。我们共同确定了一种 pDC 依赖性稳态回路,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。

英文摘要:

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.


论文信息:

论文题目:Plasmacytoid dendritic cells control homeostasis of megakaryopoiesis

期刊名称:Nature

时间期卷:Nature volume 631, pages645–653 (2024)pages685–700 (2024)

在线时间:2024年7月10日


研究数据:

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材料方法:

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