Targeting CD22 reprograms b-cells and reverses autoimmune diabetes

Paolo Fiorina, Andrea Vergani, Shirine Dada, Mollie Jurewicz, Masie Wong, Kenneth Law, Erxi Wu, Ze Tian, Reza Abdi, Indira Guleria, Scott Rodig, Kyri Dunussi-Joannopoulos, Jeffrey Bluestone, Mohamed H. Sayegh

Research output: Contribution to journalArticle

Abstract

OBJECTIVES-To investigate a B-cell-depleting strategy to reverse diabetes in naive NOD mice. RESEARCH DESIGN AND METHODS-We targeted the CD22 receptor on B-cells of naive 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.

Original languageEnglish
Pages (from-to)3013-3024
Number of pages12
JournalDiabetes
Volume57
Issue number11
DOIs
Publication statusPublished - Nov 2008

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Type 1 Diabetes Mellitus
B-Lymphocytes
Inbred NOD Mouse
Monoclonal Antibodies
Obese Mice
Gene Expression Profiling
Regulatory T-Lymphocytes
Secondary Prevention
Islets of Langerhans
Hyperglycemia
Research Design
Lymph Nodes
T-Lymphocytes
Peptides
Therapeutics
Genes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Fiorina, P., Vergani, A., Dada, S., Jurewicz, M., Wong, M., Law, K., ... Sayegh, M. H. (2008). Targeting CD22 reprograms b-cells and reverses autoimmune diabetes. Diabetes, 57(11), 3013-3024. https://doi.org/10.2337/db08-0420

Targeting CD22 reprograms b-cells and reverses autoimmune diabetes. / Fiorina, Paolo; Vergani, Andrea; Dada, Shirine; Jurewicz, Mollie; Wong, Masie; Law, Kenneth; Wu, Erxi; Tian, Ze; Abdi, Reza; Guleria, Indira; Rodig, Scott; Dunussi-Joannopoulos, Kyri; Bluestone, Jeffrey; Sayegh, Mohamed H.

In: Diabetes, Vol. 57, No. 11, 11.2008, p. 3013-3024.

Research output: Contribution to journalArticle

Fiorina, P, Vergani, A, Dada, S, Jurewicz, M, Wong, M, Law, K, Wu, E, Tian, Z, Abdi, R, Guleria, I, Rodig, S, Dunussi-Joannopoulos, K, Bluestone, J & Sayegh, MH 2008, 'Targeting CD22 reprograms b-cells and reverses autoimmune diabetes', Diabetes, vol. 57, no. 11, pp. 3013-3024. https://doi.org/10.2337/db08-0420
Fiorina P, Vergani A, Dada S, Jurewicz M, Wong M, Law K et al. Targeting CD22 reprograms b-cells and reverses autoimmune diabetes. Diabetes. 2008 Nov;57(11):3013-3024. https://doi.org/10.2337/db08-0420
Fiorina, Paolo ; Vergani, Andrea ; Dada, Shirine ; Jurewicz, Mollie ; Wong, Masie ; Law, Kenneth ; Wu, Erxi ; Tian, Ze ; Abdi, Reza ; Guleria, Indira ; Rodig, Scott ; Dunussi-Joannopoulos, Kyri ; Bluestone, Jeffrey ; Sayegh, Mohamed H. / Targeting CD22 reprograms b-cells and reverses autoimmune diabetes. In: Diabetes. 2008 ; Vol. 57, No. 11. pp. 3013-3024.
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AU - Tian, Ze

AU - Abdi, Reza

AU - Guleria, Indira

AU - Rodig, Scott

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