{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:50:00Z","timestamp":1790700600318,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,10,6]],"date-time":"2014-10-06T00:00:00Z","timestamp":1412553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Belgian Fund for Medical Scientific Research (FNRS)"},{"name":"Fonds L\u00c3\u00a9on Fr\u00c3\u00a9d\u00c3\u00a9ricq (University of Liege)"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Human papillomavirus (<jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>) infection, particularly type 16, is causally associated with cancer of the uterine cervix, which mainly develops at the squamocolumnar (<jats:styled-content style=\"fixed-case\">SC<\/jats:styled-content>) junction. The progression of cervical <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content> infections into (pre)neoplastic lesions suggests that viral antigens are not adequately recognized by innate immunity or presented to the adaptive immune system. Members of the defensin family have recently been found to inhibit viral and bacterial pathogens, to stimulate the migration of immune cells and to play a role in anticancer responses. In the present study, we focused on the poorly characterized human <jats:italic>\u03b1<\/jats:italic>\u2010defensin 5 (<jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content>\u20105) and its possible role in these processes. We showed that <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content>\u20105 was able to prevent <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content> virion entry into cervical keratinocytes and to influence adaptive immunity. Indeed, this peptide specifically induced the chemoattraction and proliferation of both activated T lymphocytes and immature dendritic cells in a <jats:styled-content style=\"fixed-case\">CCR2<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">CCR6<\/jats:styled-content>\u2010dependent manner and stimulated the infiltration of these professional antigen\u2010presenting cells in a (pre)neoplastic epithelium transplanted <jats:italic>in vivo<\/jats:italic> in immunodeficient mice. No chemotactic effect was observed with plasmacytoid dendritic cells, macrophages or natural killer cells. Proliferative and angiogenic effects of <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content>\u20105 were also assessed <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. However there was a striking regional disparity in expression of <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content>\u20105, being prominent in ectocervical, vaginal and vulvar neoplasia, while absent, or nearly so, in the cervical <jats:styled-content style=\"fixed-case\">SC<\/jats:styled-content> junction. Taken together, these results suggest one possible explanation for why the <jats:styled-content style=\"fixed-case\">SC<\/jats:styled-content> junction is uniquely vulnerable to both high\u2010risk <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content> infection (via reduced <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content>\u20105 expression and viral entry) and progression of neoplasia (via altered cell\u2010mediated immune responses and altered microenvironment). Copyright \u00a9 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd<\/jats:p>","DOI":"10.1002\/path.4435","type":"journal-article","created":{"date-parts":[[2014,9,5]],"date-time":"2014-09-05T06:25:30Z","timestamp":1409898330000},"page":"464-477","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Altered <i>\u03b1<\/i>\u2010defensin 5 expression in cervical squamocolumnar junction: implication in the formation of a viral\/tumour\u2010permissive microenvironment"],"prefix":"10.1002","volume":"234","author":[{"given":"Pascale","family":"Hubert","sequence":"first","affiliation":[{"name":"Laboratory of Experimental Pathology, GIGA\u2010Cancer University of Liege  Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludivine","family":"Herman","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Pathology, GIGA\u2010Cancer University of Liege  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