中文摘要:
血小板穩(wěn)態(tài)對于血管完整性和免疫防御至關(guān)重要提高。盡管通過分裂巨核細(xì)胞(MKs;血小板生成)形成血小板的過程已得到廣泛研究,但其祖細(xì)胞(巨核細(xì)胞生成)不斷補充MKs庫所需的細(xì)胞和分子機(jī)制仍不清楚形式。在這里共創美好,我們使用活體成像來追蹤巨核生成細(xì)胞在幾天內(nèi)的動態(tài)推動並實現。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)測骨髓中的凋亡 MK 并將 IFNα 輸送到 MK 生態(tài)位覆蓋範圍,從而觸發(fā) MK 祖細(xì)胞的局部按需增殖和成熟優化程度。這種依賴于 pDC 的反饋回路對于穩(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器5奮勇向前。我們發(fā)現(xiàn)取得明顯成效,病毒誘導(dǎo)的 pDC 激活會干擾它們作為巨核生成穩(wěn)態(tài)傳感器的功能。因此貢獻力量,SARS-CoV-2 激活 pDC 會導(dǎo)致過度的巨核生成。我們共同確定了一種 pDC 依賴性穩(wěn)態(tài)回路大幅拓展,該回路涉及先天免疫感應(yīng)和炎癥介質(zhì)的需求適應(yīng)釋放發行速度,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
時間期卷:Nature volume 631, pages645–653 (2024)pages685–700 (2024)
在線時間:2024年7月10日
研究數(shù)據(jù):
材料方法:
靶點科技(北京)有限公司
地址:中關(guān)村生命科學(xué)園北清創(chuàng)意園2-4樓2層
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