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We previously reported that individuals with VWS have increased risk of wound healing complications following cleft repair compared with individuals with nonsyndromic orofacial clefts (nonsyndromic cleft lip and palate\u2014NSCLP). In vitro, absence of IRF6 leads to impaired keratinocyte migration and embryonic wound healing. However, there is currently no data on tissue repair in adult animals and cells with reduced levels of IRF6 like in VWS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Excisional wounds of <jats:italic>Irf6<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> and wild\u2010type animals were analyzed 4 and 7\u2009days post\u2010wounding. Although all wounds were reepithelialized after 7\u2009days, the epidermal and wound volume of repaired wounds was larger in <jats:italic>Irf6<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup>. These data were supported by increased keratinocyte proliferation in the neoformed epidermis and a less mature granulation tissue with increased cytokine levels. This effect was not cell autonomous, as <jats:italic>Irf6<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> neonatal keratinocytes in vitro did not exhibit defects in scratch wound closure or proliferation. Keratinocytes from individuals with VWS also migrated similarly to keratinocytes from NSCLP individuals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These data support a role for IRF6 in wound healing by regulating keratinocyte proliferation, granulation tissue maturation, and cytokine levels.<\/jats:p><\/jats:sec>","DOI":"10.1002\/dvdy.134","type":"journal-article","created":{"date-parts":[[2019,11,14]],"date-time":"2019-11-14T03:45:07Z","timestamp":1573703107000},"page":"509-522","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Interferon regulatory factor 6 is required for proper wound healing in vivo"],"prefix":"10.1002","volume":"249","author":[{"given":"Lindsey","family":"Rhea","sequence":"first","affiliation":[{"name":"Department of Anatomy and Cell Biology The University of Iowa  Iowa City Iowa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franklin J.","family":"Canady","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The University of Iowa  Iowa City Iowa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Le","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The University of Iowa  Iowa City Iowa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tanner","family":"Reeb","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology The University of Iowa  Iowa City Iowa"},{"name":"Interdisciplinary Graduate Program in Genetics The University of Iowa  Iowa City Iowa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John W.","family":"Canady","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Surgery The University of Iowa  Iowa City Iowa"},{"name":"Department of Surgery The University of Iowa  Iowa City Iowa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah S. 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