HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ma, L. Articles by Lu, L. Search for Related Content PubMed PubMed Citation Articles by Ma, L. Articles by Lu, L. Social Bookmarking                What's this?

Prevention of Diabetes in NOD Mice by Administration of Dendritic Cells Deficient in Nuclear Transcription Factor-B Activity

¹ Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania
² Diabetes Institute, Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania
³ Department of Molecular Genetics and Biochemistry, University of Pittsburgh, Pittsburgh, Pennsylvania
⁴ Division of Immunogenetics, Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania

Abnormalities of dendritic cells (DCs) have been identified in type 1 diabetic patients and in nonobese diabetic (NOD) mice that are associated with augmented nuclear transcription factor (NF)-B activity. An imbalance that favors development of the immunogenic DCs may predispose to the disease, and restoration of the balance by administration of DCs deficient in NF-B activity may prevent diabetes. DCs propagated from NOD mouse bone marrow and treated with NF-B–specific oligodeoxyribonucleotide (ODN) in vitro (NF-B ODN DC) were assessed for efficacy in prevention of diabetes development in vivo. Gel shift assay with DC nuclear extracts confirmed specific inhibition of NF-B DNA binding by NF-B ODN. The costimulatory molecule expression, interleukin (IL)-12 production, and immunostimulatory capacity in presenting allo- and islet-associated antigens by NF-B ODN DC were significantly suppressed. NF-B ODN renders DCs resistant to lipopolysaccharide stimulation. Administration of 2 x 10⁶ NF-B ODN DCs into NOD mice aged 6–7 weeks effectively prevented the onset of diabetes. T-cells from pancreatic lymph nodes of NF-B ODN DC–treated animals exhibited hyporesponsiveness to islet antigens with low production of interferon- and IL-2. These findings provide novel insights into the mechanisms of autoimmune diabetes and may lead to development of novel preventive strategies.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				Y. Huang, I. J. Fugier-Vivier, T. Miller, M. J. Elliott, H. Xu, L. D. Bozulic, P. M. Chilton, and S. T. Ildstad Plasmacytoid Precursor Dendritic Cells From NOD Mice Exhibit Impaired Function: Are They a Component of Diabetes Pathogenesis? Diabetes, September 1, 2008; 57(9): 2360 - 2370. [Abstract] [Full Text] [PDF]

				F. Moore, S. Buonocore, E. Aksoy, N. Ouled-Haddou, S. Goriely, E. Lazarova, F. Paulart, C. Heirman, E. Vaeremans, K. Thielemans, et al. An Alternative Pathway of NF-{kappa}B Activation Results in Maturation and T Cell Priming Activity of Dendritic Cells Overexpressing a Mutated I{kappa}B{alpha} J. Immunol., February 1, 2007; 178(3): 1301 - 1311. [Abstract] [Full Text] [PDF]

				R. J. Carmody, Q. Ruan, H.-C. Liou, and Y. H. Chen Essential Roles of c-Rel in TLR-Induced IL-23 p19 Gene Expression in Dendritic Cells J. Immunol., January 1, 2007; 178(1): 186 - 191. [Abstract] [Full Text] [PDF]

				M. J. Perone, S. Bertera, Z. S. Tawadrous, W. J. Shufesky, J. D. Piganelli, L. G. Baum, M. Trucco, and A. E. Morelli Dendritic Cells Expressing Transgenic Galectin-1 Delay Onset of Autoimmune Diabetes in Mice J. Immunol., October 15, 2006; 177(8): 5278 - 5289. [Abstract] [Full Text] [PDF]

				T. Raine, P. Zaccone, P. Mastroeni, and A. Cooke Salmonella typhimurium Infection in Nonobese Diabetic Mice Generates Immunomodulatory Dendritic Cells Able to Prevent Type 1 Diabetes J. Immunol., August 15, 2006; 177(4): 2224 - 2233. [Abstract] [Full Text] [PDF]

				M. I. Iruretagoyena, S. E. Sepulveda, J. P. Lezana, M. Hermoso, M. Bronfman, M. A. Gutierrez, S. H. Jacobelli, and A. M. Kalergis Inhibition of Nuclear Factor-{kappa}B Enhances the Capacity of Immature Dendritic Cells to Induce Antigen-Specific Tolerance in Experimental Autoimmune Encephalomyelitis J. Pharmacol. Exp. Ther., July 1, 2006; 318(1): 59 - 67. [Abstract] [Full Text] [PDF]

				S. Noso, H. Ikegami, T. Fujisawa, Y. Kawabata, K. Asano, Y. Hiromine, M. Tsurumaru, S. Sugihara, I. Lee, E. Kawasaki, et al. Genetic Heterogeneity in Association of the SUMO4 M55V Variant With Susceptibility to Type 1 Diabetes Diabetes, December 1, 2005; 54(12): 3582 - 3586. [Abstract] [Full Text] [PDF]

				R. J. Steptoe, J. M. Ritchie, L. K. Jones, and L. C. Harrison Autoimmune Diabetes Is Suppressed by Transfer of Proinsulin-Encoding Gr-1+ Myeloid Progenitor Cells That Differentiate In Vivo Into Resting Dendritic Cells Diabetes, February 1, 2005; 54(2): 434 - 442. [Abstract] [Full Text] [PDF]

				P. L. Podolin, J. F. Callahan, B. J. Bolognese, Y. H. Li, K. Carlson, T. G. Davis, G. W. Mellor, C. Evans, and A. K. Roshak Attenuation of Murine Collagen-Induced Arthritis by a Novel, Potent, Selective Small Molecule Inhibitor of I{kappa}B Kinase 2, TPCA-1 (2-[(Aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide), Occurs via Reduction of Proinflammatory Cytokines and Antigen-Induced T Cell Proliferation J. Pharmacol. Exp. Ther., January 1, 2005; 312(1): 373 - 381. [Abstract] [Full Text] [PDF]

				J. Machen, J. Harnaha, R. Lakomy, A. Styche, M. Trucco, and N. Giannoukakis Antisense Oligonucleotides Down-Regulating Costimulation Confer Diabetes-Preventive Properties to Nonobese Diabetic Mouse Dendritic Cells J. Immunol., October 1, 2004; 173(7): 4331 - 4341. [Abstract] [Full Text] [PDF]