IL-17 immunity in human type 1 diabetes

J Honkanen, JK Nieminen, R Gao… - The Journal of …, 2010 - journals.aai.org
J Honkanen, JK Nieminen, R Gao, K Luopajarvi, HM Salo, J Ilonen, M Knip, T Otonkoski…
The Journal of Immunology, 2010journals.aai.org
Th17 immunity has been shown to regulate autoimmune diabetes in mice. IL-17
neutralization prevented development of diabetes when given postinitiation of insulitis but
not earlier, suggesting interference with the effector phase of the disease. Islet-cell Ag-
specific Th17 cells converted into IFN-γ–secreting Th1-like cells and caused diabetes in
mice recipients. The role of IL-17 in human type 1 diabetes (T1D) is, however, not
established. In this study, we show upregulation of Th17 immunity in peripheral blood T cells …
Abstract
Th17 immunity has been shown to regulate autoimmune diabetes in mice. IL-17 neutralization prevented development of diabetes when given postinitiation of insulitis but not earlier, suggesting interference with the effector phase of the disease. Islet-cell Ag-specific Th17 cells converted into IFN-γ–secreting Th1-like cells and caused diabetes in mice recipients. The role of IL-17 in human type 1 diabetes (T1D) is, however, not established. In this study, we show upregulation of Th17 immunity in peripheral blood T cells from children with T1D. This was characterized by increased IL-17 secretion and expression of IL-17, IL-22, and retinoic acid-related orphan receptor C isoform 2, but also FOXP3 transcripts upon T cell activation in vitro. Also, circulating memory CD4 cells from children with T1D showed the same pattern of IL-17, IL-22 and FOXP3 mRNA upregulation, indicating IL-17 pathway activation in vivo. IL-17–positive T cells appeared to be CD4+ cells expressing TCR-αβ and CCR6, and a subpopulation showed coproduction of IFN-γ. Given the Th17 immunity in T1D, we demonstrated that IL-17 had detrimental effects on human islet cells in vitro; it potentiated both inflammatory and proapoptotic responses. Our findings highlight the role of IL-17 immunity in the pathogenesis of human T1D and point to a potential therapeutic strategy.
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