IL-33 Effect on Quantitative Changes of CD4CD25FOXP3 Regulatory T Cells in Children with Type 1 Diabetes.

IL-33 is an IL-1 cytokine family member, with ability to induce both Th1 and Th2 immune responses. It binds to ST2 receptor, whose deficiency is associated with enhanced inflammatory response. The most recent studies have shown the immunoregulatory effect of IL-33 on Tregs in animal models. As type 1 diabetes is an autoimmune, inflammatory disease, where Treg defects have been described, we aimed to analyze the influence of recombinant IL-33 on quantitative properties of regulatory CD4CD25FOXP3 T cells. CD4CD25FOXP3 as well as CD4CD25FOXP3ST2 Tregs were analyzed by flow cytometry. In a group of patients with type 1 diabetes IL-33 treatment induced regulatory CD4CD25FOXP3 cell frequencies as well as upregulating the surface expression of ST2 molecule. In addition, the number of CD4CD25FOXP3 cells carrying ST2 receptor increased significantly. Similar effect was observed in case of the FOXP3 expression. We did not observe any significant changes in IL-33 treated cells of healthy controls. The level of ST2 was higher in serum of patients with type 1 diabetes in comparison to their healthy counterparts. We propose that IL-33 becomes an additional immunostimulatory factor used to induce Treg expansion in future clinical trials of adoptive therapy in type 1 diabetes.