{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T12:14:13Z","timestamp":1761394453941,"version":"3.40.2"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2014,4,1]],"date-time":"2014-04-01T00:00:00Z","timestamp":1396310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The autoimmune diabetic syndrome of the BioBreeding diabetes\u2013prone (BBDP) rat is a polygenic disease that resembles in many aspects human type 1 diabetes (T1D). A successful approach to gain insight into the mechanisms underlying genetic associations in autoimmune diseases has been to identify and map disease-related subphenotypes that are under simpler genetic control than the full-blown disease. In this study, we focused on the \u03b2 cell overexpression of Ccl11 (Eotaxin), previously postulated to be diabetogenic in BBDR rats, a BBDP-related strain. We tested the hypothesis that this trait is genetically determined and contributes to the regulation of diabetes in BBDP rats. Similar to the BBDR strain, we observed a time-dependent, insulitis-independent pancreatic upregulation of Ccl11 in BBDP rats when compared with T1D-resistant ACI.1u.lyp animals. Through linkage analysis of a cross-intercross of these two parental strains, this trait was mapped to a region on chromosome 12 that overlaps Iddm30. Linkage results were confirmed by phenotypic assessment of a novel inbred BBDP.ACI-Iddm30 congenic line. As expected, the Iddm30 BBDP allele is associated with a significantly higher pancreatic expression of Ccl11; however, the same allele confers resistance to T1D. Analysis of islet-infiltrating T cells in Iddm30 congenic BBDP animals revealed that overexpression of pancreatic Ccl11, a prototypical Th2 chemokine, is associated with an enrichment in Th2 CD4+ T cells within the insulitic lesions. These results indicate that, in the BBDP rat, Iddm30 controls T1D susceptibility through both the regulation of Ccl11 expression in \u03b2 cells and the subsequent Th1\/Th2 balance within islet-infiltrating T lymphocytes.<\/jats:p>","DOI":"10.4049\/jimmunol.1302383","type":"journal-article","created":{"date-parts":[[2014,3,20]],"date-time":"2014-03-20T05:23:45Z","timestamp":1395293025000},"page":"3645-3653","source":"Crossref","is-referenced-by-count":7,"title":["<i>Iddm30<\/i> Controls Pancreatic Expression of <i>Ccl11<\/i> (<i>Eotaxin<\/i>) and the Th1\/Th2 Balance within the Insulitic Lesions"],"prefix":"10.1093","volume":"192","author":[{"given":"Gary Y C","family":"Chao","sequence":"first","affiliation":[{"name":"Sunnybrook Research Institute , Toronto, Ontario M4N 3M5,","place":["Canada"]},{"name":"Department of Immunology, University of Toronto , Toronto, Ontario M5S 1A8,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert H","family":"Wallis","sequence":"additional","affiliation":[{"name":"Sunnybrook Research Institute , Toronto, Ontario M4N 3M5,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leili","family":"Marandi","sequence":"additional","affiliation":[{"name":"Sunnybrook Research Institute , Toronto, Ontario M4N 3M5,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terri","family":"Ning","sequence":"additional","affiliation":[{"name":"Sunnybrook Research Institute , Toronto, Ontario M4N 3M5,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janice","family":"Sarmiento","sequence":"additional","affiliation":[{"name":"Sunnybrook Research Institute , Toronto, Ontario M4N 3M5,","place":["Canada"]},{"name":"Department of Immunology, University of Toronto , Toronto, Ontario M5S 1A8,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew D","family":"Paterson","sequence":"additional","affiliation":[{"name":"Program in Genetics and Genome Biology, Hospital for Sick Children , Toronto, Ontario M5G 1L7,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philippe","family":"Poussier","sequence":"additional","affiliation":[{"name":"Sunnybrook Research Institute , Toronto, Ontario M4N 3M5,","place":["Canada"]},{"name":"Department of Immunology, University of Toronto , Toronto, Ontario M5S 1A8,","place":["Canada"]},{"name":"Faculty of Medicine, University of Toronto , Toronto, Ontario M5S 1A8,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2014,4,15]]},"reference":[{"key":"2025032404231227000_r1","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1002\/(SICI)1099-0895(199607)12:2<103::AID-DMR157>3.0.CO;2-2","article-title":"The BB\/Wor rat and the balance hypothesis of autoimmunity","volume":"12","author":"Mordes","year":"1996","journal-title":"Diabetes Metab. 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Pract."},{"key":"2025032404231227000_r36","first-page":"349","article-title":"Large increase of cytotoxic\/suppressor T-lymphoblasts and eosinophils around manifestation of diabetes in BB rats","volume":"3","author":"K\u00fcrner","year":"1986","journal-title":"Diabetes Res."},{"key":"2025032404231227000_r37","doi-asserted-by":"crossref","first-page":"7275","DOI":"10.4049\/jimmunol.177.10.7275","article-title":"Evidence of a functional role for mast cells in the development of type 1 diabetes mellitus in the BioBreeding rat","volume":"177","author":"Geoffrey","year":"2006","journal-title":"J. Immunol."},{"key":"2025032404231227000_r38","doi-asserted-by":"crossref","first-page":"2511","DOI":"10.4049\/jimmunol.162.5.2511","article-title":"Islet-specific Th1, but not Th2, cells secrete multiple chemokines and promote rapid induction of autoimmune diabetes","volume":"162","author":"Bradley","year":"1999","journal-title":"J. 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Biol. Chem."},{"key":"2025032404231227000_r50","doi-asserted-by":"crossref","first-page":"6876","DOI":"10.4049\/jimmunol.163.12.6876","article-title":"Activation of eotaxin gene transcription by NF-kappa B and STAT6 in human airway epithelial cells","volume":"163","author":"Matsukura","year":"1999","journal-title":"J. Immunol."},{"key":"2025032404231227000_r51","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1159\/000049502","article-title":"Eotaxin-1-deficient mice develop airway eosinophilia and airway hyperresponsiveness","volume":"126","author":"Tomkinson","year":"2001","journal-title":"Int. Arch. Allergy Immunol."},{"key":"2025032404231227000_r52","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1084\/jem.178.1.87","article-title":"Interleukin 4 reverses T cell proliferative unresponsiveness and prevents the onset of diabetes in nonobese diabetic mice","volume":"178","author":"Rapoport","year":"1993","journal-title":"J. Exp. 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