Disruption of the Jnk2 (Mapk9) gene reduces destructive insulitis and diabetes in a mouse model of type I diabetes.

The c-Jun NH2-terminal kinase isoform (JNK) 1 is implicated in type 2 diabetes However, a potential role for the JNK2 protein kinase in diabetes has not been established. Here, we demonstrate that JNK2 may play an important role in type 1 (insulin-dependent) diabetes that is caused by autoimmune destruction of β cells. Studies of nonobese diabetic mice demonstrated that disruption of the Mapk9 gene (which encodes the JNK2 protein kinase) decreased destructive insulitis and reduced disease progression to diabetes. CD4+ T cells from JNK2-deficient nonobese diabetic mice produced less IFN-&#x03B3 but significantly increased amounts of IL-4 and IL-5. indicating polarization toward the TH2 phenotype. This role of JNK2 to control the Thl/Th2 balance of the immune response represents a mechanism of protection against autoimmune diabetes. We conclude that JNK protein kinases may have important roles in diabetes, including functions of JNK1 in type 2 diabetes and JNK2 in type 1 diabetes. [ABSTRACT FROM AUTHOR]