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 journalJournal articleResearchpeer-review

Harvard

Funda, D, Fundova, P, Hansen, AK & Buschard, KS 2014, 'Prevention or early cure of type 1 diabetes by intranasal administration of gliadin in NOD mice', PLOS ONE, vol. 9, no. 4, e94530. https://doi.org/10.1371/journal.pone.0094530

APA

Funda, D., Fundova, P., Hansen, A. K., & Buschard, K. S. (2014). Prevention or early cure of type 1 diabetes by intranasal administration of gliadin in NOD mice. PLOS ONE, 9(4), [e94530]. https://doi.org/10.1371/journal.pone.0094530

Vancouver

Funda D, Fundova P, Hansen AK, Buschard KS. Prevention or early cure of type 1 diabetes by intranasal administration of gliadin in NOD mice. PLOS ONE. 2014;9(4). e94530. https://doi.org/10.1371/journal.pone.0094530

Author

Funda, David ; Fundova, Petra ; Hansen, Axel Kornerup ; Buschard, Karsten Stig. / Prevention or early cure of type 1 diabetes by intranasal administration of gliadin in NOD mice. In: PLOS ONE. 2014 ; Vol. 9, No. 4.

Bibtex

@article{e95c1ef61dd549b08a97b8a426d3c5a8,
title = "Prevention or early cure of type 1 diabetes by intranasal administration of gliadin in NOD mice",
abstract = "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.",
keywords = "Faculty of Health and Medical Sciences, Diabetes Mellitus, Type 1, Animal model, NOD mus, gluten, Vaccination, regulatory immunity",
author = "David Funda and Petra Fundova and Hansen, {Axel Kornerup} and Buschard, {Karsten Stig}",
year = "2014",
doi = "10.1371/journal.pone.0094530",
language = "English",
volume = "9",
journal = "P L o S One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "4",

}

RIS

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 - P L o S One

JF - P L o S One

SN - 1932-6203

IS - 4

M1 - e94530

ER -

ID: 108017169