title: IL-17 silencing does not protect nonobese diabetic mice from autoimmune diabetes.
abstract: The long-held view that many autoimmune disorders are primarily driven by a Th1 response has been challenged by the discovery of Th17 cells. Since the identification of this distinct T cell subset, Th17 cells have been implicated in the pathogenesis of several autoimmune diseases, including multiple sclerosis and rheumatoid arthritis. Type 1 diabetes has also long been considered a Th1-dependent disease. In light of the emerging role for Th17 cells in autoimmunity, several recent studies investigated the potential of this subset to initiate autoimmune diabetes. However, direct evidence supporting the involvement of Th17 cells in actual pathogenesis, particularly during spontaneous onset, is lacking. In this study, we sought to directly address the role of IL-17, the cytokine by which Th17 cells are primarily characterized, in the pathogenesis of autoimmune diabetes. We used lentiviral transgenesis to generate NOD mice in which IL-17 is silenced by RNA interference. The loss of IL-17 had no effect on the frequency of spontaneous or cyclophosphamide-induced diabetes. In contrast, IL-17 silencing in transgenic NOD mice was sufficient to reduce the severity of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis, consistent with reports that IL-17 deficiency is protective in this experimental model of multiple sclerosis. We concluded that IL-17 is dispensable, at least in large part, in the pathogenesis of autoimmune diabetes.
authors: University of Würzburg, Würzburg, Germany.
authors: Julie
authors: J
authors: Joseph
authors: Stefan
authors: S
authors: Bittner
authors: Fabian M P
authors: FM
authors: Kaiser
authors: Heinz
authors: H
authors: Wiendl
authors: Stephan
authors: S
authors: Kissler
mesh_terms: D000818:Animals; D003520:Cyclophosphamide / Q000009:adverse effects / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000235:genetics / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000494:pharmacology; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology*; D016086:Lentivirus; D051379:Mice; D016688:Mice, Inbred NOD; D034622:RNA Interference; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D014161:Transduction, Genetic / Q000379:methods
chemical_list: D007166:Immunosuppressive Agents; D020381:Interleukin-17; D003520:Cyclophosphamide