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.
authors.affiliation: The Bartholin Instituttet, Rigshospitalet, Copenhagen, Denmark; Department of Immunology and Gnotobiology, Institute of Microbiology, v.v.i., Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: David P
authors.initials: DP
authors.lastname: Funda
authors.affiliation: The Bartholin Instituttet, Rigshospitalet, Copenhagen, Denmark; Department of Immunology and Gnotobiology, Institute of Microbiology, v.v.i., Academy of Sciences of the Czech Republic, Prague, Czech Republic; ENT Department of the 3rd Faculty of Medicine, Charles University and the Central Military Hospital, Prague, Czech Republic.
authors.forename: Petra
authors.initials: P
authors.lastname: Fundova
authors.affiliation: Section of Biomedicine, Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.
authors.forename: Axel Kornerup
authors.initials: AK
authors.lastname: Hansen
authors.affiliation: The Bartholin Instituttet, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Karsten
authors.initials: K
authors.lastname: Buschard
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005903:Gliadin / Q000008:administration & dosage* / Q000627:therapeutic use*; D005983:Glutens / Q000008:administration & dosage; D006801:Humans; D018928:Immunity, Mucosal; D018655:Lymphocyte Count; D008221:Lymphoid Tissue / Q000276:immunology / Q000473:pathology; D016688:Mice, Inbred NOD
chemical_list: D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D005983:Glutens; D005903:Gliadin
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