{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T11:48:06Z","timestamp":1791114486494,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2001,11,5]],"date-time":"2001-11-05T00:00:00Z","timestamp":1004918400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2002,2,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We have addressed the notion that the initiation and progression of human papillomavirus associated cancer of the uterine cervix are associated with alterations of Langerhans cells (LC) within the mucosal squamous epithelium. Since the transformation zone (TZ) of the cervix is the site where the majority of squamous intraepithelial lesions (SIL) are initiated, in contrast to the exocervix, we decided to investigate the influence of the local microenvironment within the TZ on the function and density of LC. We show that the TZ is associated with a significant reduction in the density of immature LC (CD1a\/LAG) compared to the exocervix. In contrast, the development of SILs is attributed with a relative increased density of immature LC, compared to the TZ. Furthermore, we show that this variability in LC density is correlated with a differential expression of TNF\u03b1 and MIP3\u03b1 within the micro\u2010environment of the TZ and SILs. Both TZ and SIL epithelium\u2010derived LC, in the presence of allogeneic PBMC, induced lower levels of proliferation and IL2 production and higher levels of the immunosuppressive cytokine IL10 in comparison to the exocervix. Nevertheless, the epithelium\u2010derived LC in SILs exhibits a reduction in their functional activity, relative to the TZ. Together our studies suggest that the immunosurveillance within the epithelium of the TZ may be intrinsically perturbed due to the altered expression of chemokines\/cytokines and the concomitant diminished density of LC. Furthermore, following HPV infection and the development of SILs, the function of LC may be further incapacitated by viral associated mechanisms. \u00a9 2001 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.10084","type":"journal-article","created":{"date-parts":[[2002,9,11]],"date-time":"2002-09-11T01:24:43Z","timestamp":1031707483000},"page":"654-659","source":"Crossref","is-referenced-by-count":87,"title":["Influence of the mucosal epithelium microenvironment on Langerhans cells: Implications for the development of squamous intraepithelial lesions of the cervix"],"prefix":"10.1002","volume":"97","author":[{"given":"Sandra L.","family":"Giannini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascale","family":"Hubert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Doyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"Boniver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Delvenne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2001,11,5]]},"reference":[{"key":"e_1_2_6_2_2","first-page":"1167","article-title":"Genetic analysis of in vitro progression of human papillomavirus\u2010transfected human cervical cells","volume":"53","author":"Chen TM","year":"1993","journal-title":"Cancer Res"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910570612"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.283.8.1031"},{"key":"e_1_2_6_5_2","first-page":"6243","article-title":"Analysis of interleukin 6 gene expression in cervical neoplasia using quantitative polymerase chain reaction assay: evidence for enhanced interleukin 6 gene expression in invasive carcinoma","volume":"54","author":"Tartour E","year":"1994","journal-title":"Cancer Res"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9896(199803)184:3<283::AID-PATH25>3.0.CO;2-K"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.1998.00639.x"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.1999.00826.x"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.171.4.979"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.11.2019"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004030050144"},{"key":"e_1_2_6_12_2","doi-asserted-by":"crossref","first-page":"5761","DOI":"10.4049\/jimmunol.159.12.5761","article-title":"Induction of IL\u201010 synthesis by human keratinocytes through CD23 ligation: a cyclic adenosine 3\u2032,5\u2032\u2010monophosphate\u2010dependent mechanism","volume":"159","author":"Becherel PA","year":"1997","journal-title":"J Immunol"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.2.373"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.190.12.1755"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5439.525"},{"key":"e_1_2_6_16_2","first-page":"403","article-title":"Expression of keratins 1, 6, 15, 16, and 20 in normal cervicalepithelium, squamous metaplasia, cervical intraepithelial neoplasia, and cervical carcinoma","volume":"142","author":"Smedts F","year":"1993","journal-title":"Am J Pathol"},{"key":"e_1_2_6_17_2","first-page":"117","article-title":"Site and origin of squamous cervical cancer: a histomorphologic study","volume":"62","author":"Burghardt E","year":"1983","journal-title":"Obstet Gynecol"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00203736"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1201425"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.1985.tb03080.x"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.1983.tb08935.x"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.33.4.901-905.1995"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12455849"},{"key":"e_1_2_6_24_2","doi-asserted-by":"crossref","first-page":"2148","DOI":"10.4049\/jimmunol.150.6.2148","article-title":"Accessory cell function of keratinocytes for superantigens. 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