Ethyl pyruvate treatment enhances regulatory T cell proliferation and function in type 1 diabetes

Abstract

Type 1 diabetes (T1D) is an autoimmune disease in which a strong inflammatory response causes insulin-producing pancreatic β-cell death. Ethyl pyruvate (EP), a stable pyruvate derivate, has exerted antioxidant and anti-inflammatory properties in several disease models. To test its therapeutic potential in T1D, EP was administered intraperitoneally to C57BL/6 mice with multiple low-dose streptozotocin (STZ)-induced T1D.

EP treatment decreased T1D incidence and reduced the infiltration of cells into the pancreatic islets. Еx vivo analysis by flow cytometry showed that the EP treatment didn’t change the number of immune cells in the spleen, pancreatic lymph nodes (PLN) or pancreatic mononuclear infiltrates (PMNI), nor the relative percentages of Th1, Th17 and Th2 cells. However, EP treatment increased the levels of regulatory T cells (Treg) in PLN and PMNI. After the EP treatment, all PLN Treg were GITR+CD127-, and an increase was noted in the percentage of CD101+Treg, indicating a stronger suppressive activity. That was confirmed by an in vitro suppression assay, in which Treg from EP treated mice showed a higher capacity to supress effector T cell proliferation. The number of CXCR3+Treg and the presence of CD11а and CD62L per cell increased, which might imply an increase in Treg migration into the pancreas. However, a rise in the presence of Кi67+Treg suggested that EP treatment also promotes Treg proliferation. These results show that EP treatment reduces T1D incidence in C57BL/6 mice by enhancing Treg proliferation, suppressive capacity, and recruitment into the pancreas