RT Journal Article T1 Neutrophil expressed CD47 regulates CD11b/CD18- dependent neutrophil transepithelial migration in the intestine in vivo A1 Azcutia Criado, Verónica A1 Kelm, Matthias A1 Luissint, Anny-Claude A1 Boerner, Kevin A1 Flemming, Sven A1 Quiros, Miguel A1 Newton, Gail A1 Nusrat, Asma A1 Luscinskas, Francis W. A1 Parkos, Charles A. AB Dysregulated neutrophil (PMN) transmigration across epithelial surfaces (TEpM) significantly contributes to chronic inflammatory diseases, yet mechanisms defining this process remain poorly understood. In the intestine, uncontrolled PMN TEpM is a hallmark of disease flares in ulcerative colitis. Previous in vitro studies directed at identifying molecular determinants that mediate TEpM have shown that plasma membrane proteins including CD47 and CD11b/CD18 play key roles in regulating PMN TEpM across monolayers of intestinal epithelial cells. Here, we show that CD47 modulates PMN TEpM in vivo using an ileal loop assay. Importantly, using novel tissue-specific CD47 knockout mice and in vitro approaches, we report that PMN-expressed, but not epithelial-expressed CD47 plays a major role in regulating PMN TEpM. We show that CD47 associates with CD11b/CD18 in the plasma membrane of PMN, and that loss of CD47 results in impaired CD11b/CD18 activation. In addition, in vitro and in vivo studies using function blocking antibodies support a role of CD47 in regulating CD11b-dependent PMN TEpM and chemotaxis. Taken together, these findings provide new insights for developing approaches to target dysregulated PMN infiltration in the intestine. Moreover, tissuespecific CD47 knockout mice constitute an important new tool to study contributions of cells expressing CD47 to inflammation in vivo. PB Springer Nature YR 2020 FD 2020 LK https://hdl.handle.net/20.500.14352/117484 UL https://hdl.handle.net/20.500.14352/117484 LA eng NO Azcutia, Veronica, et al. «Neutrophil Expressed CD47 Regulates CD11b/CD18-Dependent Neutrophil Transepithelial Migration in the Intestine in Vivo». Mucosal Immunology, vol. 14, n.o 2, marzo de 2021, pp. 331-41. DOI.org (Crossref), https://doi.org/10.1038/s41385-020-0316-4 NO National Institutes of Health (US) NO Crohn's and Colitis Foundation (US) DS Docta Complutense RD 12 abr 2025