中文摘要：

血小板穩(wěn)態(tài)對(duì)于血管完整性和免疫防御至關(guān)重要。盡管通過(guò)分裂巨核細(xì)胞（MKs;血小板生成）形成血小板的過(guò)程已得到廣泛研究，但其祖細(xì)胞（巨核細(xì)胞生成）不斷補(bǔ)充MKs庫(kù)所需的細(xì)胞和分子機(jī)制仍不清楚。在這里，我們使用活體成像來(lái)追蹤巨核生成細(xì)胞在幾天內(nèi)的動(dòng)態(tài)。我們將漿細(xì)胞樣樹突狀細(xì)胞 （pDC） 確定為穩(wěn)態(tài)傳感器，可監(jiān)測(cè)骨髓中的凋亡 MK 并將 IFNα 輸送到 MK 生態(tài)位，從而觸發(fā) MK 祖細(xì)胞的局部按需增殖和成熟。這種依賴于 pDC 的反饋回路對(duì)于穩(wěn)態(tài)和壓力下的 MK 和血小板穩(wěn)態(tài)至關(guān)重要。pDC 最出名的是它們能夠作為病毒感染的警戒檢測(cè)器5。我們發(fā)現(xiàn)，病毒誘導(dǎo)的 pDC 激活會(huì)干擾它們作為巨核生成穩(wěn)態(tài)傳感器的功能。因此，SARS-CoV-2 激活 pDC 會(huì)導(dǎo)致過(guò)度的巨核生成。我們共同確定了一種 pDC 依賴性穩(wěn)態(tài)回路，該回路涉及先天免疫感應(yīng)和炎癥介質(zhì)的需求適應(yīng)釋放，以維持巨核細(xì)胞譜系的穩(wěn)態(tài)。

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.

論文信息：

論文題目：Plasmacytoid dendritic cells control homeostasis of megakaryopoiesis

期刊名稱：Nature

時(shí)間期卷：Nature volume 631, pages645–653 (2024)pages685–700 (2024)

在線時(shí)間：2024年7月10日

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