Reprogrammed neutrophils with impaired transit mechanics drive multi-organ capillary stalling after stroke

Droux, J.; Husson, J.; Glueck, C.; Preuss, H.; Del Campo Fonseca, A.; Bergaglio, T.; Otto, L. B.; Sparano, C.; Hoesli, L.; Glandorf, L.; Palmier, B.; Tugues, S.; Razansky, D.; Margaill, I.; Greter, M.; Ahmed, D.; Casanova Acebes, M.; Nishimura, N.; Schaffer, C. B.; Hidalgo, A.; Weber, B.; Wegener, S.; EL AMKI, M.

doi:10.64898/2026.02.10.705064

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bioRxiv · 10.64898/2026.02.10.705064

Reprogrammed neutrophils with impaired transit mechanics drive multi-organ capillary stalling after stroke

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Abstract

Beyond the focal brain lesion, stroke causes systemic complications including cardiac failure, pneumonia, renal injury, and sustained immune dysfunction. The source of this multiorgan vulnerability remains unresolved. By imaging over 16,000 vessels of healthy, inflamed and ischemic brains, we identify a circulating neutrophil subpopulation reprogrammed by stroke into a pathological stalling phenotype, occluding capillaries in the brain, heart, kidneys, retina and lungs. Combining transcriptomics, genetic models, integrated microfluidics, cell mechanics assays, and in vivo imaging, we show that this subpopulation exhibits an atypical morphology, increased actin polymerization, and heightened adhesion that impair transit through capillary networks. This phenotype is present in patients with stroke, transmissible by adoptive transfer, and selectively sensitive to inhibition of the Src-family kinase Fgr. Both pharmacological and genetic inactivation of Fgr normalize neutrophil adhesion, reduce capillary stalls, and improve neurological recovery after stroke. These findings identify immune cell transit failure as a systemic driver of post-stroke pathology and a therapeutic target to improve both cerebral and multiorgan outcomes.

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Droux, J., Husson, J., Glueck, C., Preuss, H., Del Campo Fonseca, A., Bergaglio, T., Otto, L. B., Sparano, C., Hoesli, L., Glandorf, L., Palmier, B., Tugues, S., Razansky, D., Margaill, I., Greter, M., Ahmed, D., Casanova Acebes, M., Nishimura, N., Schaffer, C. B., Hidalgo, A., Weber, B., Wegener, S., EL AMKI, M.. 2026-02-11. Reprogrammed neutrophils with impaired transit mechanics drive multi-organ capillary stalling after stroke. https://doi.org/10.64898/2026.02.10.705064

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