The significance of tyrosine kinase 2 gene in encephalomyocarditis-D virus-induced diabetes as studied in Tyk2 gene knockout mice (P6334)

Abstract Type 1 diabetes mellitus results form progressive loss of pancreatic β cells. The virus, as one of environmental factors, has been long considered to play a role in the development of type 1 diabetes. The D variant of encephalomyocarditis (EMC-D) virus induced susceptible strain of mice to become type 1 diabetes. We have already reported that innate immunity may play an important role in protection against EMC-D virus-induced diabetes (Arch Virol, 2008). In the present study, we analyzed the role of Tyk2 gene in the pathogenic mechanism of EMC-D virus-induced diabetes by using Tyk2 gene knockout (KO) mice. Tyk2 gene KO C57BL/6J mice, mouse strain resistant to EMC-D virus-induced diabetes, developed diabetes. In order to examine whether Tyk2 gene expression was important in parenchymal or immune cells to protect against EMC-D virus-induced diabetes, we developed splenic chimera mice. Tyk2 gene expression was important in parenchymal cells, but not in spleen cells, to resist against EMC-D virus-induced diabetes. Consistently, mice specifically expressed Tyk2 gene only in pancreatic β cells prevented EMC-D virus-induced diabetes. These observations suggest that Tyk2 gene expressed in pancreatic β cells plays a significant role in preventing EMC-D virus-induced diabetes in mice.