ArticleThe Journal of clinical investigation1998
Local expression of immunoregulatory IL-12p40 gene prolonged syngeneic islet graft survival in diabetic NOD mice.
Article in The Journal of clinical investigation, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 67 citations in OpenAlex.
- Anti-cytokine therapies in T1D: Concepts and strategies.Clinical immunology (Orlando, Fla.) · 2013Review
- Immuno-regulatory function of indoleamine 2,3 dioxygenase through modulation of innate immune responses.PloS one · 2013Article
- Genetic vaccination for re-establishing T-cell tolerance in type 1 diabetes.Human vaccines · 2011Review
- Current status and prospects for gene and cell therapeutics for type 1 diabetes mellitus.Reviews in endocrine & metabolic disorders · 2003Review
- Role of cytokines in the pathogenesis of autoimmune diabetes mellitus.Reviews in endocrine & metabolic disorders · 2003Review
- Gene- and cell-based therapeutics for type I diabetes mellitus.Gene therapy · 2003Review
- Antigen-specific T cell-mediated gene therapy in collagen-induced arthritis.The Journal of clinical investigation · 2001Article
- Immunotherapy of immune-mediated diabetes. Present and future.Clinical reviews in allergy & immunology · 2000Review
- Immunotherapy of spontaneous type 1 diabetes in nonobese diabetic mice by systemic interleukin-4 treatment employing adenovirus vector-mediated gene transfer.Gene therapy · 2000Article
- Interleukin (IL)-4 is a major regulatory cytokine governing bioactive IL-12 production by mouse and human dendritic cells.The Journal of experimental medicine · 2000Article
- Gene therapy in the treatment of autoimmune diseases.The Journal of clinical investigation · 2000Article
- Endogenous interleukin-12 only plays a key pathogenetic role in non-obese diabetic mouse diabetes during the very early stages of the disease.Immunology · 1999Article
- Ex vivo gene transfer of viral interleukin-10 to BB rat islets: no protection after transplantation to diabetic BB rats.Journal of cellular and molecular medicineArticle
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Local production of immunosuppressive cytokines will be one of the most suitable therapeutic strategies against organ-specific autoimmune diabetes. To establish such a new therapy, we constructed recombinant adenoviral vectors with inserted mIL-12p40 (Ad.IL-12p40) and mIL-10 (Ad.IL-10). Sufficient amounts of IL-12p40 and IL-10 were secreted by relevant adenovirus-transfected nonobese diabetic (NOD) islets. Shortly after transfection, 400 NOD islets transfected with Ad.IL-12p40 or Ad.IL-10 were transplanted under the renal capsule of a newly diabetic NOD mouse. NOD mice with IL-12p40-producing islet grafts kept normoglycemia in all of 14 grafted mice for over 4 wk after transplantation. In contrast, NOD mice with IL-10-producing islet grafts became diabetic in all of six grafted mice within 2 wk af-ter transplantation. Reverse transcription-PCR analysis revealed that local production of IL-12p40 led to the decrease of interferon-gamma and the augmentation of transforming growth factor-beta at the graft site. These results suggest that IL-12 plays an important role in the destruction of islet cells at the inflamed site of autoimmunity. Such a local blockade of IL-12 would be a useful gene therapy for human autoimmune diabetes.
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