Prevention or early cure of type 1 diabetes by intranasal administration of gliadin in NOD mice
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- Prevention or early cure of type 1 diabetes by intranasal administration of gliadin in NOD mice
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Induction of long-term tolerance to β-cell autoantigens has been investigated both in animal models and in human type 1 diabetes (T1D) in order to prevent the disease. As regards external compounds, the dietary plant protein fraction has been associated with high penetrance of the disease, whereas gluten-free diets prevent T1D in animal models. Herewith we investigated whether intranasal (i.n.) administration of gliadin or gluten may arrest the diabetogenic process. I.n. administration of gliadin to 4-week-old NOD mice significantly reduced the diabetes incidence. Similarly, the insulitis was lowered. Intranasal gliadin also rescued a fraction of prediabetic 13-week-old NOD mice from progressing to clinical onset of diabetes compared to OVA-treated controls. Vaccination with i.n. gliadin led to an induction of CD4+Foxp3+ T cells and even more significant induction of γδ T cells in mucosal, but not in non-mucosal lymphoid compartments. This prevention strategy was characterized by an increased proportion of IL-10 and a decreased proportion of IL-2, IL-4 and IFN-γ-positive CD4+Foxp3+ T cells, and IFN-γ-positive γδ T cells, preferentially in mucosal lymphoid organs. In conclusion, i.n. vaccination with gliadin, an environmental antigen with possible etiological influence in T1D, may represent a novel, safer strategy for prevention or even early cure of T1D.
Originalsprog | Engelsk |
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Artikelnummer | e94530 |
Tidsskrift | PLOS ONE |
Vol/bind | 9 |
Udgave nummer | 4 |
Antal sider | 10 |
ISSN | 1932-6203 |
DOI | |
Status | Udgivet - 2014 |
- Det Sundhedsvidenskabelige Fakultet - Diabetes Mellitus, Type 1, Animal model, NOD mus, gluten, Vaccination, regulatory immunity
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