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Nectin signaling induces formation of cell\u2013cell junctions and is required for the development of epithelial tissues, including skin. This study investigated the role of afadin in epithelial tissue development and established epithelium\u2010specific afadin\u2010deficient (<jats:styled-content style=\"fixed-case\">CKO<\/jats:styled-content>) mice. Although showing no obvious abnormality in the skin development and homeostasis, the mice showed the reduced neutrophil infiltration into the epidermis during chemical\u2010induced inflammation with 12\u2010<jats:italic>O<\/jats:italic>\u2010tetradecanoylphorbol 13\u2010acetate (<jats:styled-content style=\"fixed-case\">TPA<\/jats:styled-content>). Immunohistochemical and quantitative real\u2010time <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> analyses showed that the expression levels of cytokines including Cxcl2<jats:italic>,<\/jats:italic> Il\u20101\u03b2 and Tnf\u2010\u03b1 were reduced in <jats:styled-content style=\"fixed-case\">CKO<\/jats:styled-content> keratinocytes compared with control keratinocytes during <jats:styled-content style=\"fixed-case\">TPA<\/jats:styled-content>\u2010induced inflammation. Primary\u2010cultured skin keratinocytes from <jats:styled-content style=\"fixed-case\">CKO<\/jats:styled-content> mice also showed reduced expression of these cytokines and weak activation of Rap1 compared with those from control mice after the <jats:styled-content style=\"fixed-case\">TPA<\/jats:styled-content> treatment. These results suggested a remarkable function of afadin, which was able to enhance cytokine expression through Rap1 activation in keratinocytes during inflammation.<\/jats:p>","DOI":"10.1111\/gtc.12184","type":"journal-article","created":{"date-parts":[[2014,10,9]],"date-time":"2014-10-09T10:07:39Z","timestamp":1412849259000},"page":"842-852","source":"Crossref","is-referenced-by-count":8,"title":["Afadin requirement for cytokine expressions in keratinocytes during chemically induced inflammation in mice"],"prefix":"10.1111","volume":"19","author":[{"given":"Toshiyuki","family":"Yoshida","sequence":"first","affiliation":[{"name":"Institute of Advanced Biomedical Engineering and Science Tokyo Women's Medical University 8\u20101 Kawada\u2010cho Shinjuku\u2010ku Tokyo 162\u20108666 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takanori","family":"Iwata","sequence":"additional","affiliation":[{"name":"Institute of Advanced Biomedical Engineering and Science Tokyo Women's Medical University 8\u20101 Kawada\u2010cho Shinjuku\u2010ku Tokyo 162\u20108666 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshimi","family":"Takai","sequence":"additional","affiliation":[{"name":"Division of Pathogenetic Signaling Department of Biochemistry and Molecular Biology Kobe University Graduate School of Medicine 1\u20105\u20106 Minatojima\u2010minamimachi Chuo\u2010ku Kobe Hyogo 650\u20100047 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Walter","family":"Birchmeier","sequence":"additional","affiliation":[{"name":"Max Delbr\u00fcck Center for Molecular Medicine Robert\u2010R\u00f6ssle\u2010Str. 10 Berlin\u2010Buch 13125 Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masayuki","family":"Yamato","sequence":"additional","affiliation":[{"name":"Institute of Advanced Biomedical Engineering and Science Tokyo Women's Medical University 8\u20101 Kawada\u2010cho Shinjuku\u2010ku Tokyo 162\u20108666 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teruo","family":"Okano","sequence":"additional","affiliation":[{"name":"Institute of Advanced Biomedical Engineering and Science Tokyo Women's Medical University 8\u20101 Kawada\u2010cho Shinjuku\u2010ku Tokyo 162\u20108666 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,10,9]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn243"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.07.003"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2012.01.009"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3405"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pathol.2.010506.091944"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E12-10-0736"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0463.2011.02832.x"},{"key":"e_1_2_6_9_1","doi-asserted-by":"crossref","first-page":"3144","DOI":"10.4049\/jimmunol.140.9.3144","article-title":"Neutrophil leukocyte emigration induced by endotoxin. 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