Th17/Th1 axis polarization is mediated by IL-1 receptor in type 1 diabetes murine model (123.13)

Abstract

Abstract Introduction: Autoimmune diseases including type 1 diabetes (T1D) are thought to have a Th1/Th17 bias, but the underlying mechanisms driving the differentiation and activation of these pathogenic T cells has been investigated. Recently, the IL-1beta has been shown to regulate Th17 cell differentiation through of the expression of the transcription factor RORγt. Objective: For this reason, we addressed the respective IL-1 receptor (IL-1R) role in the TD1. Methods: IL-1R deficient mice and their wild-type (C57BL/6) were inoculated intraperitoneally with 40mg/Kg of streptozotocin for 5 consecutive days. Blood glucose levels and body weight were monitored weekly. The pancreatic lymph nodes (PLN) were removed to assess the Th17 and Th1 frequency by flow cytometry. Results: Diabetic IL-1R deficient mice developed lower hyperglycemia with only 50% of mice becoming diabetic. In agreement, mice lacking IL-1R have reduced inflammatory infiltrate (insulitis) and augmented insulin content into pancreatic islets by second week. In addition, the IL-1R deficiency caused a decrease in IL-17 and IFN-γ-producing CD4+ T cell population in pancreatic lymph nodes (PLN). The IL-17, IL-6, TNF-α, IFN-γ levels were not altered, but IL-10 and IL-4 levels were higher in pancreatic tissue of diabetic IL-1R deficient mice. Conclusion: These results suggest that IL-1receptor promotes the Th17/Th1 skewing in the PLN and possibly contributes to pancreatic islet damage during the T1D onset.