IL-33 Effect on Quantitative Changes of CD4+CD25highFOXP3+ 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 in vitro influence of recombinant IL-33 on quantitative properties of regulatory CD4(+)CD25(high)FOXP3(+) T cells. CD4(+)CD25(high)FOXP3(+) as well as CD4(+)CD25(high)FOXP3(+)ST2(+) Tregs were analyzed by flow cytometry. In a group of patients with type 1 diabetes in vitro IL-33 treatment induced regulatory CD4(+)CD25(high)FOXP3(+) cell frequencies as well as upregulating the surface expression of ST2 molecule. In addition, the number of CD4(+)CD25(high)FOXP3(+) 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.