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Complex innate host response mechanisms have evolved whereby potentially harmful pathogens are recognized by multiple host pattern recognition receptors (<jats:styled-content style=\"fixed-case\">PRRs<\/jats:styled-content>), yet understanding of <jats:styled-content style=\"fixed-case\">PRR<\/jats:styled-content> function, or dysfunction, in the context of chronic wounds remains limited. <jats:styled-content style=\"fixed-case\">NOD2<\/jats:styled-content>, a cytoplasmic <jats:styled-content style=\"fixed-case\">PRR<\/jats:styled-content>, has been strongly implicated in chronic inflammation of the gut, where loss\u2010of\u2010function mutations have been linked to Crohn's disease; however, cutaneous Nod2 function remains poorly characterized. Here we demonstrate an important role for Nod2 in murine skin wound healing. Cutaneous Nod2 is induced in key wound cell types in response to injury. In the absence of Nod2, mice display a substantial delay in acute wound repair associated with epithelial and inflammatory changes. Specifically, <jats:italic>Nod2<\/jats:italic>\u2010null mice display altered epidermal migration and proliferation, an initial delay in neutrophil recruitment associated with decreased expression of the chemokine receptor <jats:styled-content style=\"fixed-case\">CXCR2<\/jats:styled-content>, and reduced numbers of alternatively activated macrophages (Ym1<jats:sup>+<\/jats:sup> cells). Somewhat surprisingly, these <jats:italic>Nod2<\/jats:italic>\u2010null phenotypes were associated with little or no expression change in other <jats:styled-content style=\"fixed-case\">PRRs<\/jats:styled-content>, even though compensatory mechanisms have been shown to exist. In this study we show that healing in <jats:italic><jats:styled-content style=\"fixed-case\">TLR2<\/jats:styled-content><\/jats:italic>\u2010null mice was essentially normal. These findings reveal a novel intrinsic role for Nod2 in cutaneous wound repair in addition to its role in recognizing invading pathogens.<\/jats:p>","DOI":"10.1002\/path.4095","type":"journal-article","created":{"date-parts":[[2012,9,6]],"date-time":"2012-09-06T07:08:08Z","timestamp":1346915288000},"page":"121-131","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Nod2 deficiency impairs inflammatory and epithelial aspects of the cutaneous wound\u2010healing response"],"prefix":"10.1002","volume":"229","author":[{"given":"Laura","family":"Campbell","sequence":"first","affiliation":[{"name":"Healing Foundation Centre University of Manchester  UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen","family":"Williams","sequence":"additional","affiliation":[{"name":"Healing Foundation Centre University of Manchester  UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel 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