Targeting CD22 Reprograms B-Cells and Reverses Autoimmune Diabetes

Targeting CD22 Reprograms B-Cells and Reverses Autoimmune Diabetes

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Targeting CD22 Reprograms B-Cells and Reverses Autoimmune Diabetes

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