We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Prevention of diabetes in NOD mice by administration of dendritic cells deficient in nuclear transcription factor-kappaB activity.
- Authors
Ma, Linlin; Linlin Ma; Qian, Shiguang; Shiguang Qian; Xiaoyan Liang; Liang, Xiaoyan; Wang, Lianfu; Lianfu Wang; Woodward, Jennifer E.; Giannoukakis, Nick; Robbins, Paul D.; Bertera, Suzanne; Trucco, Massimo; Fung, John J.; Lina Lu; Lu, Lina
- 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)-kappaB 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-kappaB activity may prevent diabetes. DCs propagated from NOD mouse bone marrow and treated with NF-kappaB-specific oligodeoxyribonucleotide (ODN) in vitro (NF-kappaB 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-kappaB DNA binding by NF-kappaB ODN. The costimulatory molecule expression, interleukin (IL)-12 production, and immunostimulatory capacity in presenting allo- and islet-associated antigens by NF-kappaB ODN DC were significantly suppressed. NF-kappaB ODN renders DCs resistant to lipopolysaccharide stimulation. Administration of 2 x 10(6) NF-kappaB ODN DCs into NOD mice aged 6-7 weeks effectively prevented the onset of diabetes. T-cells from pancreatic lymph nodes of NF-kappaB ODN DC-treated animals exhibited hyporesponsiveness to islet antigens with low production of interferon-gamma and IL-2. These findings provide novel insights into the mechanisms of autoimmune diabetes and may lead to development of novel preventive strategies.
- Subjects
DENDRITIC cells; DIABETES prevention; TRANSCRIPTION factors; DNA metabolism; ANIMAL experimentation; CELLULAR immunity; COMPARATIVE studies; CYTOKINES; ISLANDS of Langerhans; TYPE 1 diabetes; RESEARCH methodology; MEDICAL cooperation; MICE; NUCLEOTIDES; RESEARCH; T cells; PHENOTYPES; DNA-binding proteins; EVALUATION research; TRANSPLANTATION of organs, tissues, etc.; PREVENTION
- Publication
Diabetes, 2003, Vol 52, Issue 8, p1976
- ISSN
0012-1797
- Publication type
journal article