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Immunol."],"abstract":"<jats:p>The actin-related protein (ARP) 2\/3 complex, essential for organizing and nucleating branched actin filaments, is required for several cellular immune processes, including cell migration and granule exocytosis. Recently, genetic defects in ARPC1B, a subunit of this complex, were reported. Mutations in <jats:italic>ARPC1B<\/jats:italic> result in defective ARP2\/3-dependent actin filament branching, leading to a combined immunodeficiency with severe inflammation. <jats:italic>In vitro<\/jats:italic>, neutrophils of these patients showed defects in actin polymerization and chemotaxis, whereas adhesion was not altered under static conditions. Here we show that under physiological flow conditions human ARPC1B-deficient neutrophils were able to transmigrate through TNF-\u03b1-pre-activated endothelial cells with a decreased efficiency and, once transmigrated, showed definite impairment in subendothelial crawling. Furthermore, severe locomotion and migration defects were observed in a 3D collagen matrix and a perfusable vessel-on-a-chip model. These data illustrate that neutrophils employ ARP2\/3-independent steps of adhesion strengthening for transmigration but rely on ARP2\/3-dependent modes of migration in a more complex multidimensional environment.<\/jats:p>","DOI":"10.3389\/fimmu.2021.678030","type":"journal-article","created":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T08:51:00Z","timestamp":1622451060000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Defective Neutrophil Transendothelial Migration and Lateral Motility in ARPC1B Deficiency Under Flow Conditions"],"prefix":"10.3389","volume":"12","author":[{"given":"Lanette","family":"Kempers","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelien G. 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