1. Th1/Th17 plasticity is a marker of advanced β cell autoimmunity and impaired glucose tolerance in humans
- Author
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Outi Vaarala, Kirsi Alahuhta, Linnea Reinert-Hartwall, Henna Kallionpää, Olli Simell, Natalya Dorshakova, Sami Oikarinen, Harri M. Salo, Robert Moulder, Sergei Mokurov, Riitta Veijola, Jorma Ilonen, Elena Kuzmicheva, Samppa J. Ryhänen, Juliane Weber, Suvi M. Virtanen, Vladimir Petrov, Matti Koski, Helis Janson, Helena Ahlfors, Terhi Ruohtula, Anu-Maaria Hämäläinen, Vallo Tillmann, Elena Shakurova, Janne Nieminen, Tatyana Varlamova, Hanna Honkanen, Janne K. Nieminen, Taina Härkönen, Tatyana Karapetyan, Erika von Mutius, Tiit Salum, Essi Laajala, Kristiina Luopajärvi, Jarno Honkanen, Heikki Hyöty, Riitta Lahesmaa, Katriina Koski, Marcus C. de Goffau, Aleksandr Peet, Raivo Uibo, Mikael Knip, Kristi Alnek, Marina Isakova, Svetlana Pylova, Harri Lähdesmäki, Hermie J. M. Harmsen, Gjalt W. Welling, Valentina Ulich, Svetlana Markova, Anne Ormisson, Anita Kondrashova, Minna Kiviniemi, Microbes in Health and Disease (MHD), and Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)
- Subjects
Male ,Immunology ,Cell ,Autoimmunity ,medicine.disease_cause ,T-Lymphocytes, Regulatory ,Impaired glucose tolerance ,Ikaros Transcription Factor ,Interferon-gamma ,Downregulation and upregulation ,Immunity ,Diabetes mellitus ,Insulin-Secreting Cells ,Glucose Intolerance ,medicine ,Immunology and Allergy ,Humans ,Child ,Cells, Cultured ,Autoantibodies ,Type 1 diabetes ,business.industry ,Interleukin-17 ,Autoantibody ,Interleukin-9 ,Th1 Cells ,medicine.disease ,Up-Regulation ,medicine.anatomical_structure ,Diabetes Mellitus, Type 1 ,Child, Preschool ,Disease Progression ,Th17 Cells ,Female ,business ,Biomarkers - Abstract
Upregulation of IL-17 immunity and detrimental effects of IL-17 on human islets have been implicated in human type 1 diabetes. In animal models, the plasticity of Th1/Th17 cells contributes to the development of autoimmune diabetes. In this study, we demonstrate that the upregulation of the IL-17 pathway and Th1/Th17 plasticity in peripheral blood are markers of advanced β cell autoimmunity and impaired β cell function in human type 1 diabetes. Activated Th17 immunity was observed in the late stage of preclinical diabetes in children with β cell autoimmunity and impaired glucose tolerance, but not in children with early β cell autoimmunity. We found an increased ratio of IFN-γ/IL-17 expression in Th17 cells in children with advanced β cell autoimmunity, which correlated with HbA1c and plasma glucose concentrations in an oral glucose tolerance test, and thus impaired β cell function. Low expression of Helios was seen in Th17 cells, suggesting that Th1/Th17 cells are not converted thymus-derived regulatory T cells. Our results suggest that the development of Th1/Th17 plasticity may serve as a biomarker of disease progression from β cell autoantibody positivity to type 1 diabetes. These data in human type 1 diabetes emphasize the role of Th1/Th17 plasticity as a potential contributor to tissue destruction in autoimmune conditions.
- Published
- 2014