Disruption of the Jnk2 (Mapk9) gene reduces destructive insulitis and diabetes in a mouse model of type I diabetes
Authors
Jaeschke, AnjaRincon, Mercedes
Doran, Beth
Reilly, Judith
Neuberg, Donna S.
Greiner, Dale L.
Shultz, Leonard D.
Rossini, Aldo A.
Flavell, Richard A.
Davis, Roger J.
UMass Chan Affiliations
Cancer CenterDepartment of Medicine, Division of Diabetes
Howard Hughes Medical Institute and Program in Molecular Medicine
Document Type
Journal ArticlePublication Date
2005-05-04Keywords
AnimalsApoptosis
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
Metadata
Show full item recordAbstract
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.Source
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
DOI
10.1073/pnas.0502143102Permanent Link to this Item
http://hdl.handle.net/20.500.14038/38924PubMed ID
15867147Related Resources
ae974a485f413a2113503eed53cd6c53
10.1073/pnas.0502143102