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dc.contributor.authorSutherland, Andrew P
dc.contributor.authorVan Belle, Tom
dc.contributor.authorWurster, Andrea L.
dc.contributor.authorSuto, Akira
dc.contributor.authorMichaud, Monia
dc.contributor.authorZhang, Dorothy
dc.contributor.authorGrusby, Michael J.
dc.contributor.authorvon Herrath, Matthias
dc.date.accessioned2010-11-04T20:51:18Z
dc.date.issued2009
dc.identifier.citationSutherland, Andrew P.R., Tom Van Belle, Andrea L. Wurster, Akira Suto, Monia Michaud, Dorothy Zhang, Michael J. Grusby, and Matthias von Herrath. 2009. Interleukin-21 Is Required for the Development of Type 1 Diabetes in NOD Mice. Diabetes 58(5): 1144-1155.en_US
dc.identifier.issn0012-1797en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4522609
dc.description.abstractOBJECTIVE: Interleukin (IL)-21 is a type 1 cytokine that has been implicated in the pathogenesis of type 1 diabetes via the unique biology of the nonobese diabetic (NOD) mouse strain. The aim of this study was to investigate a causal role for IL-21 in type 1 diabetes. RESEARCH DESIGN AND METHODS: We generated IL-21R–deficient NOD mice and C57Bl/6 mice expressing IL-21 in pancreatic β-cells, allowing the determination of the role of insufficient and excessive IL-21 signaling in type 1 diabetes. RESULTS: Deficiency in IL-21R expression renders NOD mice resistant to insulitis, production of insulin autoantibodies, and onset of type 1 diabetes. The lymphoid compartment in IL-21R−/− NOD is normal and does not contain an increased regulatory T-cell fraction or diminished effector cytokine responses. However, we observed a clear defect in autoreactive effector T-cells in IL-21R−/− NOD by transfer experiments. Conversely, overexpression of IL-21 in pancreatic β-cells induced inflammatory cytokine and chemokines, including IL-17A, IL17F, IFN-γ, monocyte chemoattractant protein (MCP)-1, MCP-2, and interferon-inducible protein-10 in the pancreas. The ensuing leukocytic infiltration in the islets resulted in destruction of β-cells and spontaneous type 1 diabetes in the normally diabetes-resistant C57Bl/6 and NOD × C57Bl/6 backgrounds. CONCLUSIONS: This work provides demonstration of the essential prodiabetogenic activities of IL-21 on diverse genetic backgrounds (NOD and C57BL/6) and indicates that IL-21 blockade could be a promising strategy for interventions in human type 1 diabetes.en_US
dc.language.isoen_USen_US
dc.publisherAmerican Diabetes Associationen_US
dc.relation.isversionofdoi:10.2337/db08-0882en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2671036/pdf/en_US
dash.licenseLAA
dc.subjectimmunology and transplantationen_US
dc.titleInterleukin-21 Is Required for the Development of Type 1 Diabetes in NOD Miceen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalDiabetesen_US
dash.depositing.authorGrusby, Michael J.
dc.date.available2010-11-04T20:51:18Z
dash.affiliation.otherSPH^Immunology and Infectious Diseases Immunologyen_US
dash.affiliation.otherSPH^Dean's Office Administrationen_US
dc.identifier.doi10.2337/db08-0882*
dash.contributor.affiliatedMichaud, Monia
dash.contributor.affiliatedSutherland, Andrew P
dash.contributor.affiliatedGrusby, Michael


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