Disruption of the Jnk2 (Mapk9) gene reduces destructive insulitis and diabetes in a mouse model of type I diabetes
Howard Hughes Medical Institute and Program in Molecular Medicine; Department of Medicine, Division of Diabetes; Cancer Center
Animals; Apoptosis; CD4-Positive T-Lymphocytes; Cell Differentiation; Diabetes Mellitus, Experimental; Female; *Gene Expression Regulation; Immune System; Immunohistochemistry; Insulin; Male; Mice; Mice, Inbred NOD; Mice, SCID; Mice, Transgenic; Microscopy, Fluorescence; Mitogen-Activated Protein Kinase 9; Phenotype; Protein Isoforms; Th1 Cells; Th2 Cells; Time Factors
Life Sciences | Medicine and Health Sciences
The c-Jun NH(2)-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 beta 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-gamma but significantly increased amounts of IL-4 and IL-5, indicating polarization toward the Th2 phenotype. This role of JNK2 to control the Th1/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.
DOI of Published Version
Proc Natl Acad Sci U S A. 2005 May 10;102(19):6931-5. Epub 2005 May 2. Link to article on publisher's site
Proceedings of the National Academy of Sciences of the United States of America
Jaeschke, Anja; Rincon, Mercedes; Doran, Beth; Reilly, Judith; Neuberg, Donna S.; Greiner, Dale L.; Shultz, Leonard D.; Rossini, Aldo A.; Flavell, Richard A.; and Davis, Roger J., "Disruption of the Jnk2 (Mapk9) gene reduces destructive insulitis and diabetes in a mouse model of type I diabetes" (2005). Open Access Articles. 1756.