NDLI: Iddm30 controls pancreatic expression of Ccl11 (Eotaxin) and the Th1/Th2 balance within the insulitic lesions.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Poussier, Philippe Wallis, Robert H. Marandi, Leili Paterson, Andrew D. Sarmiento, Janice Ning, Terri Chao, Gary Y. C.
Description	Author Affiliation: Chao GY ( Sunnybrook Research Institute, Toronto, Ontario M4N 3M5, Canada)
Abstract	The autoimmune diabetic syndrome of the BioBreeding diabetes-prone (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 ß 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 ß cells and the subsequent Th1/Th2 balance within islet-infiltrating T lymphocytes.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	8
Volume Number	192
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2014-04-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Chemokine Ccl11 Genetics Diabetes Mellitus, Type 1 Immunology Gene Expression Regulation Genetic Loci Pancreas Metabolism Th1-th2 Balance Animals Breeding Epistasis, Genetic Gene Expression Genetic Linkage Genotype Insulin-secreting Cells Phenotype Rats, Inbred Bb Transcription, Genetic Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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