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. / Funda, David; Fundova, Petra; Hansen, Axel Kornerup; Buschard, Karsten Stig.
In: PLOS ONE, Vol. 9, No. 4, e94530, 2014.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Prevention or early cure of type 1 diabetes by intranasal administration of gliadin in NOD mice
AU - Funda, David
AU - Fundova, Petra
AU - Hansen, Axel Kornerup
AU - Buschard, Karsten Stig
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - Faculty of Health and Medical Sciences
KW - Diabetes Mellitus, Type 1
KW - Animal model
KW - NOD mus
KW - gluten
KW - Vaccination
KW - regulatory immunity
U2 - 10.1371/journal.pone.0094530
DO - 10.1371/journal.pone.0094530
M3 - Journal article
C2 - 24728138
VL - 9
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 4
M1 - e94530
ER -
ID: 108017169