Prevention of diabetes in NOD mice by administration of dendritic cells deficient in nuclear transcription factor-κB activity

Linlin Ma, Shiguang Qian, Xiaoyan Liang, Lianfu Wang, Jennifer E. Woodward, Nick Giannoukakis, Paul D. Robbins, Suzanne Bertera, Massimo Trucco, John J. Fung, Lina Lu

Research output: Contribution to journalArticle

77 Scopus citations

Abstract

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)-κB 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-κB activity may prevent diabetes. DCs propagated from NOD mouse bone marrow and treated with NF-κB-specific oligodeoxyribonucleotide (ODN) in vitro (NF-κB 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-κB DNA binding by NF-κB ODN. The costimulatory molecule expression, interleukin (IL)-12 production, and immunostimulatory capacity in presenting allo- and islet-associated antigens by NF-κB ODN DC were significantly suppressed. NF-κB ODN renders DCs resistant to lipopolysaccharide stimulation. Administration of 2 × 106 NF-κB ODN DCs into NOD mice aged 6-7 weeks effectively prevented the onset of diabetes. T-cells from pancreatic lymph nodes of NF-KB ODN DC-treated animals exhibited hyporesponsiveness to islet antigens with low production of interferon-γ and IL-2. These findings provide novel insights into the mechanisms of autoimmune diabetes and may lead to development of novel preventive strategies.

Original languageEnglish (US)
Pages (from-to)1976-1985
Number of pages10
JournalDiabetes
Volume52
Issue number8
DOIs
StatePublished - Aug 1 2003

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    Ma, L., Qian, S., Liang, X., Wang, L., Woodward, J. E., Giannoukakis, N., Robbins, P. D., Bertera, S., Trucco, M., Fung, J. J., & Lu, L. (2003). Prevention of diabetes in NOD mice by administration of dendritic cells deficient in nuclear transcription factor-κB activity. Diabetes, 52(8), 1976-1985. https://doi.org/10.2337/diabetes.52.8.1976