ArticleThe Journal of experimental medicine2008
Innocuous IFNgamma induced by adjuvant-free antigen restores normoglycemia in NOD mice through inhibition of IL-17 production.
Article in The Journal of experimental medicine, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.
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Who cites it
97 citing papers in PubMed, 179 citations in OpenAlex.
- Gut microbiota and pathobiont exposure influences disease incidence in non-obese diabetic mice.Frontiers in microbiology · 2026Article
- T helper 17 cells and interleukin-17 immunity in type 1 diabetes: From pathophysiology to targeted immunotherapies.World journal of diabetes · 2025Review
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- Polyphenols: immunonutrients tipping the balance of immunometabolism in chronic diseases.Frontiers in immunology · 2024Review
- PPARs at the crossroads of T cell differentiation and type 1 diabetes.Frontiers in immunology · 2023Review
- 2D and 3D cultured human umbilical cord-derived mesenchymal stem cell-conditioned medium has a dual effect in type 1 diabetes model in rats: immunomodulation and beta-cell regeneration.Inflammation and regeneration · 2022Article
- Article
- Role of the adaptive immune system in diabetic kidney disease.Journal of diabetes investigation · 2022Review
- Syngeneic bone marrow transplantation in combination with PI3K inhibitor reversed hyperglycemia in later-stage streptozotocin-induced diabetes.Annals of translational medicine · 2021Article
- Formation of pancreatic β-cells from precursor cells contributes to the reversal of established type 1 diabetes.Cellular immunology · 2021Article
- Arrest in the Progression of Type 1 Diabetes at the Mid-Stage of Insulitic Autoimmunity Using an Autoantigen-Decorated All-Frontiers in immunology · 2021Article
- Two to Tango: Dialogue between Adaptive and Innate Immunity in Type 1 Diabetes.Journal of diabetes research · 2020Review
- Salivary and serum interleukin-17A and interleukin-18 levels in patients with type 2 diabetes mellitus with and without periodontitis.PloS one · 2020Article
- Peroxiredoxin 6 Attenuates Alloxan-Induced Type 1 Diabetes Mellitus in Mice and Cytokine-Induced Cytotoxicity in RIN-m5F Beta Cells.Journal of diabetes research · 2020Article
- eIF5A inhibition influences T cell dynamics in the pancreatic microenvironment of the humanized mouse model of Type 1 Diabetes.Scientific reports · 2019Article
- CD122 blockade restores immunological tolerance in autoimmune type 1 diabetes via multiple mechanisms.JCI insight · 2018Article
- Recovery of Cardiac Remodeling and Dysmetabolism by Pancreatic Islet Injury Improvement in Diabetic Rats after Yacon Leaf Extract Treatment.Oxidative medicine and cellular longevity · 2018Article
- Human Gingiva-Derived Mesenchymal Stem Cells Ameliorate Streptozoticin-induced T1DM in mice via Suppression of T effector cells and Up-regulating Treg Subsets.Scientific reports · 2017Article
- Neutralization Versus Reinforcement of Proinflammatory Cytokines to Arrest Autoimmunity in Type 1 Diabetes.Clinical reviews in allergy & immunology · 2017Review
- MSC-derived Extracellular Vesicles Attenuate Immune Responses in Two Autoimmune Murine Models: Type 1 Diabetes and Uveoretinitis.Stem cell reports · 2017Article
37 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
The role of Th17 cells in type I diabetes (TID) remains largely unknown. Glutamic acid decarboxylase (GAD) sequence 206-220 (designated GAD2) represents a late-stage epitope, but GAD2-specific T cell receptor transgenic T cells producing interferon gamma (IFNgamma) protect against passive TID. Because IFNgamma is known to inhibit Th17 cells, effective presentation of GAD2 peptide under noninflammatory conditions may protect against TID at advanced disease stages. To test this premise, GAD2 was genetically incorporated into an immunoglobulin (Ig) molecule to magnify tolerance, and the resulting Ig-GAD2 was tested against TID at different stages of the disease. The findings indicated that Ig-GAD2 could not prevent TID at the preinsulitis phase, but delayed TID at the insulitis stage. More importantly, Ig-GAD2 sustained both clearance of pancreatic cell infiltration and beta-cell division and restored normoglycemia when given to hyperglycemic mice at the prediabetic stage. This was dependent on the induction of splenic IFNgamma that inhibited interleukin (IL)-17 production. In fact, neutralization of IFNgamma led to a significant increase in the frequency of Th17 cells, and the treatment became nonprotective. Thus, IFNgamma induced by an adjuvant free antigen, contrary to its usual inflammatory function, restores normoglycemia, most likely by localized bystander suppression of pathogenic IL-17-producing cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.