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Immunity, Corrected proof. doi:10.1016/j.immuni.2025.03.020SUMMARYThrombotic diseases remain the major cause of death and disability worldwide, and the contribution ofinflammation 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-celllevel has been lacking.Here, we reveal innate leukocyte substates with prominent thrombolytic properties by employing single-cellomics measures on human stroke thrombi. Using in vivo and in vitro thrombosis models, we propose a proresolving monocyte-neutrophil axis, combining two properties: (1) NR4A1hi non-classical monocytes acquirea 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-inducedthrombus-resolving urokinase receptor (PLAUR)+ phenotype. This immunothrombolytic axis results inthrombus resolution. Together, with this immune landscape of thrombosis, we provide a valuable resourceand introduce the concept of ‘‘immunothrombolysis’’ with broad mechanistic and translation

Author

Kami Pekayvaz, Badr Kilani

Publisher

The Authors

Published

2025

Language

EN