{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:55:55Z","timestamp":1785437755285,"version":"3.56.0"},"posted":{"date-parts":[[2026,3,27]]},"group-title":"Immunology","reference-count":54,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["R56DK140172"],"award-info":[{"award-number":["R56DK140172"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01DK140172"],"award-info":[{"award-number":["R01DK140172"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Polymorphonuclear neutrophils (PMNs) serve as frontline defenders against injury and infection, eliminating pathogens and initiating mucosal tissue repair. However, excessive PMN transepithelial migration (TEpM) contributes to chronic mucosal inflammatory disorders, including inflammatory bowel disease. PMN pro-inflammatory and pro-repair functions are regulated by incompletely defined signaling cascades involving kinases and phosphatases. Here, we determined how the protein tyrosine phosphatase CD45\/PTPRC regulates PMN trafficking and effector functions in the gut. Pharmacologic inhibition of CD45 significantly reduced PMN colonic TEpM\n                  <jats:italic>in vitr<\/jats:italic>\n                  o and\n                  <jats:italic>in vivo<\/jats:italic>\n                  and decreased intestinal PMN trafficking was observed in transgenic mice with PMN-specific deletion of CD45 (\n                  <jats:italic>\n                    MRP8-Cre;Cd45\n                    <jats:sup>fl<\/jats:sup>\n                  <\/jats:italic>\n                  <jats:sup>\/fl<\/jats:sup>\n                  ). Beyond limiting TEpM, CD45 depletion impaired key antimicrobial functions, including degranulation and phagocytosis, indicating broader effects on PMN effector activity. Importantly, recovery from dextran sodium sulfate (DSS)\u2013induced colitis and biopsy-induced colonic wounding was delayed in\n                  <jats:italic>\n                    MRP8-Cre;Cd45\n                    <jats:sup>fl<\/jats:sup>\n                  <\/jats:italic>\n                  <jats:sup>\/fl<\/jats:sup>\n                  mice, linking altered PMN function to defective mucosal healing. Mechanistically, CD45 depletion reduced surface expression of the \u03b22 integrin CD11b\/CD18 and inactivated the Src family kinase member Lyn. Together, data highlight a novel CD45\u2013CD11b\u2013Lyn signaling axis that regulates PMN trafficking and effector functions in the intestine and identify CD45 as a promising target for modulating PMN function to promote mucosal tissue repair.\n                <\/jats:p>","DOI":"10.64898\/2026.03.25.714205","type":"posted-content","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T19:55:21Z","timestamp":1774641321000},"source":"Crossref","is-referenced-by-count":0,"title":["The Protein Tyrosine Phosphatase CD45 promotes PMN Transepithelial Migration, Antimicrobial Function and Colonic Mucosal Repair"],"prefix":"10.64898","author":[{"given":"Jael","family":"Miranda","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dylan J","family":"Fink","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary S","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Hilgarth","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asma","family":"Nusrat","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles A","family":"Parkos","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer C","family":"Brazil","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026033111352801000_2026.03.25.714205v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3399"},{"issue":"25","key":"2026033111352801000_2026.03.25.714205v1.2","doi-asserted-by":"crossref","first-page":"7019","DOI":"10.1016\/j.cell.2025.11.001","article-title":"The neutrophil collective","volume":"188","year":"2025","journal-title":"Cell"},{"key":"2026033111352801000_2026.03.25.714205v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2015.63"},{"key":"2026033111352801000_2026.03.25.714205v1.4","doi-asserted-by":"crossref","unstructured":"Hayashi S , Muraleedharan CK , Oku M , Tomar S , Hogan SP , Quiros M , et al. 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