Journal Article

DZNE-2025-00615

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Immunothrombolytic monocyte-neutrophil axes dominate the single-cell landscape of human thrombosis and correlate with thrombus resolution.

Pekayvaz, K. ; Kilani, B. ; Joppich, M. ; Eivers, L. ; Brambs, S. ; Knottenberg, V. ; Akgöl, S. ; Yue, K. ; Li, L. ; Martinez-Navarro, A. ; Kaiser, R. ; Meißner, N. ; Schulz, H. ; Belz, L. ; Akhalkatsi, A. ; Stockhausen, S. ; Mueller, T. T. ; Millonig, S. ; Hartelt, L. ; Gold, C. ; Janjic, A. ; Polewka, V. ; Wendler, F. ; Droste Zu Senden, A. ; Titova, A. ; Leunig, A. ; Voelkl, M. ; Engelmann, B. ; Hernandez Petzsche, M. R. ; Boeckh-Behrens, T. ; Liebig, T. ; Winning, S. ; Fandrey, J. ; Dichgans, M.DZNE* ; Enard, W. ; Zimmer, R. ; Tiedt, S. ; Massberg, S. ; Nicolai, L. ; Stark, K.

2025
Cell Press [Cambridge, Mass.]

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Please use a persistent id in citations: doi:10.1016/j.immuni.2025.03.020

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.

Keyword(s): Humans (MeSH) ; Monocytes: immunology (MeSH) ; Monocytes: metabolism (MeSH) ; Thrombosis: immunology (MeSH) ; Thrombosis: pathology (MeSH) ; Neutrophils: immunology (MeSH) ; Neutrophils: metabolism (MeSH) ; Single-Cell Analysis (MeSH) ; Animals (MeSH) ; Mice (MeSH) ; Receptors, Interleukin-8B: metabolism (MeSH) ; Male (MeSH) ; Female (MeSH) ; Inflammation: immunology (MeSH) ; immune landscape ; immune-cell plasticity ; immunothrombolysis ; immunothrombosis ; immunothrombotic dysregulation ; innate immunity ; monocytes ; multi-omics ; neutrophils ; organ ischemia ; single-cell ; stroke ; thromboinflammation ; thrombosis ; thrombus resolution ; Receptors, Interleukin-8B

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Contributing Institute(s):

1. Vascular Cognitive Impairment & Post-Stroke Dementia (AG Dichgans)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2025

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 30 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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