{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T02:44:51Z","timestamp":1789785891109,"version":"4.0.1"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2012,12,1]],"date-time":"2012-12-01T00:00:00Z","timestamp":1354320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100008664","name":"Juvenile Diabetes Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008664","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Local abnormalities in CD8\u03ba+ DCs in the pre-diabetic NOD pancreas suggest that these DCs contribute to loss of tolerance, hallmarking the development of autoimmune diabetes.<\/jats:p>\n               <jats:p>The NOD mouse is a widely used animal model of autoimmune diabetes. Prior to the onset of lymphocytic insulitis, DCs accumulate at the islet edges. Our recent work indicated that these DCs may derive from aberrantly proliferating local precursor cells. As CD8\u03b1+ DCs play a role in tolerance induction in steady-state conditions, we hypothesized that the autoimmune phenotype might associate with deficiencies in CD8\u03b1+ DCs in the prediabetic NOD mouse pancreas. We studied CD8\u03b1+ DCs in the pancreas and pLNs of NOD and control mice, focusing on molecules associated with tolerance induction (CD103, Langerin, CLEC9A, CCR5). mRNA expression levels of tolerance-modulating cytokines were studied in pancreatic CD8\u03b1+ DCs of NOD and control mice. In the NOD pancreas, the frequency of CD8\u03b1+CD103+Langerin+ cells was reduced significantly compared with control mice. NOD pancreatic CD8\u03b1+CD103+Langerin+ DCs expressed reduced levels of CCR5, CLEC9A, and IL-10 as compared with control DCs. These alterations in the CD8\u03b1+CD103+Langerin+ DC population were not present in pLNs. We demonstrate local abnormalities in the CD8\u03b1+ DC population in the prediabetic NOD pancreas. These data suggest that abnormal differentiation of pancreatic DCs contributes to loss of tolerance, hallmarking the development of autoimmune diabetes.<\/jats:p>","DOI":"10.1189\/jlb.0312168","type":"journal-article","created":{"date-parts":[[2012,9,26]],"date-time":"2012-09-26T11:43:09Z","timestamp":1348659789000},"page":"1207-1213","source":"Crossref","is-referenced-by-count":20,"title":["Reduced numbers of dendritic cells with a tolerogenic phenotype in the prediabetic pancreas of NOD mice"],"prefix":"10.1093","volume":"92","author":[{"given":"Jojanneke M C","family":"Welzen-Coppens","sequence":"first","affiliation":[{"name":"Department of Immunology, Erasmus MC University Medical Center , Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia G","family":"van Helden-Meeuwsen","sequence":"additional","affiliation":[{"name":"Department of Immunology, Erasmus MC University Medical Center , Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter J M","family":"Leenen","sequence":"additional","affiliation":[{"name":"Department of Immunology, Erasmus MC University Medical Center , Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hemmo A","family":"Drexhage","sequence":"additional","affiliation":[{"name":"Department of Immunology, Erasmus MC University Medical Center , Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjan A","family":"Versnel","sequence":"additional","affiliation":[{"name":"Department of Immunology, Erasmus MC University Medical Center , Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,12,1]]},"reference":[{"key":"2023012312584208300_B1","first-page":"380","article-title":"The non-obese diabetic (NOD) mouse","volume":"128","author":"Leiter","year":"1987","journal-title":"Am. 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