Immunothrombolytic monocyte-neutrophil axes dominate the single-cell landscape of human thrombosis and correlate with thrombus resolution by Kami Pekayvaz, Badr Kilani ISBN 101016/JIMMUNI202503020 instant download

Immunothrombolytic monocyte-neutrophil axes dominate the single-cell landscape of human thrombosis and correlate with thrombus resolution by Kami Pekayvaz, Badr Kilani ISBN 101016/JIMMUNI202503020 instant download

SUMMARYThrombotic 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 translational implicationsat the crossroad of inflammation and thrombosis.