免疫溶栓性单核细胞-中性粒细胞轴主导着人类血栓形成的单细胞景观，并与血栓溶解相关，这一成果由大学Konstantin Stark课题组经过不懈努力而取得。2025年4月24日出版的《免疫学》杂志发表了这项成果。

课题组人员通过使用单细胞组学测量人类中风血栓，揭示了具有突出溶栓特性的先天白细胞底态。利用体内和体外血栓形成模型，课题组人员提出了一个促溶解的单核细胞-中性粒细胞轴，它结合了两个特性：(1)NR4A1^hi非经典单核细胞获得溶栓和嗜中性粒细胞趋化表型；(2)血液中性粒细胞因此通过CXCL8-CXCR1和CXCR2不断募集，形成血栓，并采用缺氧诱导的溶栓尿激酶受体(PLAUR)⁺表型。免疫溶栓轴导致血栓溶解。总之，在血栓形成的免疫景观中，课题组人员提供了有价值的抵抗，并在炎症和血栓形成的十字路口引入了具有广泛机制和翻译意义的“免疫溶栓”概念。

据介绍，血栓性疾病仍然是世界范围内死亡和残疾的主要原因，炎症的作用越来越被认识到。血栓炎症已被确定为一个关键的病理机制，但在单细胞水平上缺乏免疫细胞状态、轨迹和相互交流的无监督图谱。

附：英文原文

Title: Immunothrombolytic monocyte-neutrophil axes dominate the single-cell landscape of human thrombosis and correlate with thrombus resolution

Author: Kami Pekayvaz, Badr Kilani, Markus Joppich, Luke Eivers, Sophia Brambs, Viktoria Knottenberg, Sezer Akgl, Keyang Yue, Lukas Li, Alejandro Martinez-Navarro, Rainer Kaiser, Nina Meiner, Heiko Schulz, Larissa Belz, Anastassia Akhalkatsi, Sven Stockhausen, Tonina T. Mueller, Simon Millonig, Lea Hartelt, Christoph Gold, Aleksandar Janjic, Vivien Polewka, Franziska Wendler, Augustin Droste zu Senden, Anna Titova, Alexander Leunig, Michael Voelkl, Bernd Engelmann, Moritz R. Hernandez Petzsche, Tobias Boeckh-Behrens, Thomas Liebig, Sandra Winning, Joachim Fandrey, Martin Dichgans, Wolfgang Enard, Ralf Zimmer, Steffen Tiedt, Steffen Massberg, Leo Nicolai, Konstantin Stark

Issue&Volume: 2025-04-24

Abstract: Thrombotic diseases remain the major cause of death and disability worldwide, and the contribution of inflammation is increasingly recognized. Thromboinflammation has been identified as a key pathomechanism, but an unsupervised map of immune-cell states, trajectories, and intercommunication at a single-cell level has been lacking.

Here, we reveal innate leukocyte substates with prominent thrombolytic properties by employing single-cell omics measures on human stroke thrombi. Using in vivo and in vitro thrombosis models, we propose a pro-resolving monocyte-neutrophil axis, combining two properties: (1) NR4A1hi non-classical monocytes acquire a thrombolytic and neutrophil-chemoattractive phenotype, and (2) blood neutrophils are thereby continuously recruited to established thrombi through CXCL8-CXCR1 and CXCR2 and adopt a hypoxia-induced thrombus-resolving urokinase receptor (PLAUR)+ phenotype. This immunothrombolytic axis results in thrombus resolution. Together, with this immune landscape of thrombosis, we provide a valuable resource and introduce the concept of “immunothrombolysis” with broad mechanistic and translational implications at the crossroad of inflammation and thrombosis.

DOI: 10.1016/j.immuni.2025.03.020

Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00139-6