Megakaryocyte emperipolesis arms neutrophils via intracellular provisioning
Year: 2026
Type: preprint
Abstract: ABSTRACT Neutrophils are phenotypically heterogenous cells that mediate host defense and tissue homeostasis. Here, we identify emperipolesis – the evolutionarily conserved process by which neutrophils pass through megakaryocytes – as a phenotypically transformative route of egress from bone marrow. By intravital microscopy and 3-D histology, we show that the rapid form emperipolesis is markedly enhanced under inflammatory conditions. Neutrophils exit from megakaryocytes directly to the blood, acquiring exosomes enriched in proteins related to metabolism, migration, and immune function. This transfer induces a distinct neutrophil phenotype characterized by enhanced glycolysis, oxidative phosphorylation, cytokine release, and longevity. Correspondingly, emperipolesis-educated neutrophils display accelerated migration in vitro and in vivo . Disrupting emperipolesis does not alter circulating neutrophil abundance but impairs neutrophil infiltration into inflamed tissues, including Pseudomonas aeruginosa -infected lung. These findings establish emperipolesis as a mechanism by which megakaryocytes amplify neutrophil-mediated immunity.
Authors: Julia K. Kuehn, Geon Ho Bae, Roxane Darbousset, Frank Y. Huang, Rebecca M. Hall, Josephin E. Schiffer, Dhruv Miglani, Spoorthi Balu, Alexandra Wactor, Dorsaf Ghaloussi, Olga Barreiro, Li Guo, Andrew S. Weyrich, Simon J. Cleary, Matthias Gunzer, Yoichiro Iwakura, David P. Hoytema van Konijnenburg, Joseph E. Italiano, Mark R. Looney, Éric Boilard, Wolfgang Bergmeier, Pierre Cunin, Peter A. Nigrovic
Institutions: Boston Children's Hospital, Harvard University, German Cancer Research Center, Heidelberg University, DKFZ-ZMBH Alliance, Heidelberg Institute for Stem Cell Technology and Experimental Medicine, University of North Carolina at Chapel Hill, University of Washington, University of Utah, Bloodworks Northwest, Oklahoma Medical Research Foundation, University of California, San Francisco, King's College London, Leibniz Institute for Analytical Sciences - ISAS, University of Duisburg-Essen, Louis Pasteur Center for Medical Research, The University of Tokyo, Centre hospitalier universitaire de Québec, Université Laval, Brigham and Women's Hospital
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funders: Arthritis National Research Foundation, American Heart Association, AABB, National Scleroderma Foundation, Boehringer Ingelheim Fonds, Deutsche Forschungsgemeinschaft, National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1770065365, TRR 332: Neutrophile Granulozyten: Entwicklung, Verhalten, und Funktion, Activation-Dependent Golgi Formation and MHC I Glycosylation in Platelets during Stroke, G4810603143, G5691504833, G9000044434, G9000108119, The Centrosome as a master controller of platelet production., Understanding the Platelet-CD8+ T Cell Interactions in Sepsis, Joint Biology Consortium Resource-based Center, Child Health Research Career Development Award (CHRCDA) Program (K12)
OpenAlex ID: W7202094266