Targeting CD22 Reprograms B-Cells and Reverses Autoimmune Diabetes

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Targeting CD22 Reprograms B-Cells and Reverses Autoimmune Diabetes

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dc.contributor.author Dada, Shirine
dc.contributor.author Wong, Masie
dc.contributor.author Law, Kenneth
dc.contributor.author Wu, Erxi
dc.contributor.author Dunussi-Joannopoulos, Kyri
dc.contributor.author Bluestone, Jeffrey
dc.contributor.author Fiorina, Paolo
dc.contributor.author Vergani, Andrea
dc.contributor.author Jurewicz, Mollie
dc.contributor.author Tian, Ze
dc.contributor.author Abdi, Reza
dc.contributor.author Guleria, Indira
dc.contributor.author Rodig, Scott J.
dc.contributor.author Sayegh, Mohamed Hassan
dc.date.accessioned 2011-12-01T16:47:12Z
dc.date.issued 2008
dc.identifier.citation Fiorina, Paolo, Andrea Vergani, Shirine Dada, Mollie Jurewicz, Masie Wong, Kenneth Law, Erxi Wu, et al. 2008. Targeting CD22 reprograms B-cells and reverses autoimmune diabetes. Diabetes 57(11): 3013-3024. en_US
dc.identifier.issn 0012-1797 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:5358770
dc.description.abstract OBJECTIVES—To investigate a B-cell–depleting strategy to reverse diabetes in naïve NOD mice. RESEARCH DESIGN AND METHODS—We targeted the CD22 receptor on B-cells of naïve NOD mice to deplete and reprogram B-cells to effectively reverse autoimmune diabetes. RESULTS—Anti-CD22/cal monoclonal antibody (mAb) therapy resulted in early and prolonged B-cell depletion and delayed disease in pre-diabetic mice. Importantly, when new-onset hyperglycemic mice were treated with the anti-CD22/cal mAb, 100% of B-cell–depleted mice became normoglycemic by 2 days, and 70% of them maintained a state of long-term normoglycemia. Early therapy after onset of hyperglycemia and complete B-cell depletion are essential for optimal efficacy. Treated mice showed an increase in percentage of regulatory T-cells in islets and pancreatic lymph nodes and a diminished immune response to islet peptides in vitro. Transcriptome analysis of reemerging B-cells showed significant changes of a set of proinflammatory genes. Functionally, reemerging B-cells failed to present autoantigen and prevented diabetes when cotransferred with autoreactive \(CD4^+\) T-cells into NOD.SCID hosts. CONCLUSIONS—Targeting CD22 depletes and reprograms B-cells and reverses autoimmune diabetes, thereby providing a blueprint for development of novel therapies to cure autoimmune diabetes. en_US
dc.language.iso en_US en_US
dc.publisher American Diabetes Association en_US
dc.relation.isversionof doi:10.2337/db08-0420 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2570398/pdf/ en_US
dash.license LAA
dc.title Targeting CD22 Reprograms B-Cells and Reverses Autoimmune Diabetes en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal Diabetes en_US
dash.depositing.author Fiorina, Paolo
dc.date.available 2011-12-01T16:47:12Z
dash.affiliation.other HMS^Pediatrics-Children's Hospital en_US
dash.affiliation.other HMS^Pediatrics-Children's Hospital en_US
dash.affiliation.other SPH^Genetics and Complex Diseases en_US
dash.affiliation.other HMS^Medicine-Brigham and Women's Hospital en_US
dash.affiliation.other HMS^Medicine-Brigham and Women's Hospital en_US

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