IL-23 leads to diabetes induction after subdiabetogenic treatment with multiple low doses of streptozotocin

Authors

  • Eric P. K. Mensah-Brown,

    1. Department of Anatomy, Faculty of Medicine and Health Sciences, UAE University,Al Ain, United Arab Emirates
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  • Allen Shahin,

    1. Department of Microbiology and Immunology, Faculty of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates
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  • Mariam Al-Shamisi,

    1. Department of Microbiology and Immunology, Faculty of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates
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  • Xiaoging Wei,

    1. Division of Immunology, Infection and inflammation, University of Glasgow, Glasgow, UK
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  • Miodrag L. Lukic

    Corresponding author
    1. Department of Microbiology and Immunology, Faculty of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates
    2. Faculty of Medicine, University of Kragujevac, Kragujevac, Serbia
    • Department of Microbiology and Immunology, Faculty of Medicine and Health Sciences, UAE University, P O Box 17666, Al Ain, United Arab Emirates, Fax: +971-3-7671966
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Abstract

IL-23, a proximal regulator of IL-17, may be a major driving force in the induction of autoimmune inflammation. We have used a model of subdiabetogenic treatment with multiple low doses of streptozotocin (MLD-STZ; 4 × 40 mg/kg body weight) in male C57BL/6 mice to study the effect of IL-23 on immune-mediated β cell damage and the development of diabetes, as evaluated by blood glucose, quantitative histology, immunohistochemistry and expression of relevant cytokines in the islets. Ten daily injections of 400 ng IL-23, starting on the first day of MLD-STZ administration led to significant and sustained hyperglycemia along with weight loss compared with controls (no IL-23), and a significant increase in the number of infiltrating cells, a lower insulin content, enhanced apoptosis, expression of IFN-γ and IL-17 (not seen in the controls) and a significant increase in the expression of TNF-α and IL-18 in the pancreatic islets. IL-23 treatment started 5 days prior to MLD-STZ administration had no effect on diabetogenesis or cytokines expression in the pancreatic islets. We provide the first evidence in an animal model that IL-23 is involved in the development of type-1 diabetes, by inducing IL-17 and possibly IFN-γ production in the target tissue.

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