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Inhibition of Th17 Cells Regulates Autoimmune Diabetesin NOD Mice Diabetes. 2009 Jun;58(6):1302-11. doi: 10.2337/db08-1113. Epub 2009 Mar 16. Objective The T helper 17 (Th17) population, a subset of CD4-positive T-cells that secrete interleukin (IL)-17, has been implicated in autoimmune diseases, including multiple sclerosis and lupus. Therapeutic agents that target the Th17 effector molecule IL-17 or directly inhibit the Th17 population (IL-25) have shown promise in animal models of autoimmunity. The role of Th17 cells in type 1 diabetes has been less clear. The effect of neutralizing anti–IL-17 and recombinant IL-25 on the development of diabetes in NOD mice, a model of spontaneous autoimmune diabetes, was investigated in this study. In an effort to both understand the impact of and reduce the negative effects of the Th17 subpopulation, a number of studies have been carried out using neutralizing anti–IL-17 antibodies. A single injection of anti–IL-17 antibody prevented inflammation and bone erosion and reduced Th17 populations in experimental rheumatoid arthritis(RA), whereas multiple doses of anti–IL-17 over 2 weeks dramatically reduced inflammatory lesions and neurological symptoms in experimental autoimmune encephalomyelitis (EAE). DESIGN AND METHODS Drug therapy Diabetes prevention Diabetes remission Diabetes recurrence after syngeneic islet transplantation Insulitis scoring. Immunofluorescence. GAD65 autoantibody assays Inhibition of Th17 cells prevents progression to diabetes in pre-diabetic animals. Drug therapy Diabetes prevention control anti-IL17 IL-25 Anti–IL-17 and IL-25 treatment reduces isletinflammation. GAD65 autoantibody assays Anti–IL-17 and IL-25 treatment prevents GAD65 autoantibody formation IL-25 treatment reduces the frequency of autoreactive Th2 and Th17 T-cells and results in the development of a Treg-enriched CD4-positive T cell population that dominantly protects against disease transfer.