{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T18:14:04Z","timestamp":1775153644483,"version":"3.50.1"},"reference-count":46,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,4,8]],"date-time":"2023-04-08T00:00:00Z","timestamp":1680912000000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["ZU377\/4\u20101"],"award-info":[{"award-number":["ZU377\/4\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["ID 375876048"],"award-info":[{"award-number":["ID 375876048"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational Med"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Closing mucosal defects to reach mucosal healing is an important goal of therapy in inflammatory bowel disease (IBD). Among other cells, monocyte\u2010derived macrophages are centrally involved in such intestinal wound healing. We had previously demonstrated that the anti\u2010\u03b14\u03b27 integrin antibody vedolizumab blocks the recruitment of non\u2010classical monocytes as biased progenitors of wound healing macrophages to the gut and delays wound healing. However, although important for the interpretation of disappointing results in recent phase III trials in IBD, the effects of the anti\u2010\u03b27 antibody etrolizumab on wound healing are unclear so far.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed the expression of etrolizumab targets on human and mouse monocyte subsets by flow cytometry and assessed their function in adhesion and homing assays. We explored wound\u2010associated monocyte recruitment dynamics with multiphoton microscopy and compared the effects of etrolizumab and vedolizumab surrogate (\u2010s) antibodies on experimental wound healing and wound\u2010associated macrophage abundance. Finally, we investigated wound healing macrophage signatures in the large intestinal transcriptome of patients with Crohn's disease treated with etrolizumab.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Human and mouse non\u2010classical monocytes expressed more \u03b1E\u03b27 integrin than classical monocytes and were a target of etrolizumab\u2010s, which blocked non\u2010classical monocyte adhesion to MAdCAM\u20101 and E\u2010Cadherin as well as gut homing in vivo. Intestinal wound healing was delayed on treatment with etrolizumab\u2010s along with a reduction of peri\u2010lesional wound healing macrophages. Wound healing macrophage signatures in the colon of patients with Crohn's disease were substantially down\u2010regulated on treatment with etrolizumab, but not with placebo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Combined blockade of \u03b1E\u03b27 and \u03b14\u03b27 with etrolizumab seems to exceed the effect of anti\u2010\u03b14\u03b27 treatment on intestinal wound healing, which might help to inform further investigations to understand the recent observations in the etrolizumab phase III trial program.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.1233","type":"journal-article","created":{"date-parts":[[2023,4,8]],"date-time":"2023-04-08T14:29:34Z","timestamp":1680964174000},"source":"Crossref","is-referenced-by-count":11,"title":["Anti\u2010\u03b27 integrin treatment impedes the recruitment on non\u2010classical monocytes to the gut and delays macrophage\u2010mediated intestinal wound healing"],"prefix":"10.1002","volume":"13","author":[{"given":"Katrin","family":"Sommer","sequence":"first","affiliation":[{"name":"Department of Medicine University Hospital Erlangen and Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg  Erlangen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin","family":"Heidbreder","sequence":"additional","affiliation":[{"name":"Department of Medicine University Hospital Erlangen and Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg  Erlangen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucas","family":"Kreiss","sequence":"additional","affiliation":[{"name":"Department of Medicine University Hospital Erlangen and Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg  Erlangen Germany"},{"name":"Institute of Medical Biotechnology Department of Chemical and Biological Engineering (CBI) 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