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

Abstract	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.
Authors	Anja Jaeschke, Mercedes Rincón, Beth Doran, Judith Reilly, Donna Neuberg, Dale L Greiner, Leonard D Shultz, Aldo A Rossini, Richard A Flavell, Roger J Davis
Journal	Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 102 Issue 19 Pg. 6931-5 (May 10 2005) ISSN: 0027-8424 [Print] United States
PMID	15867147 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Insulin Protein Isoforms Mitogen-Activated Protein Kinase 9
Topics	Animals Apoptosis CD4-Positive T-Lymphocytes (immunology) Cell Differentiation Diabetes Mellitus, Experimental (genetics) Female Gene Expression Regulation Immune System Immunohistochemistry Insulin (metabolism) Male Mice Mice, Inbred NOD Mice, SCID Mice, Transgenic Microscopy, Fluorescence Mitogen-Activated Protein Kinase 9 (genetics, physiology) Phenotype Protein Isoforms Th1 Cells (immunology) Th2 Cells (immunology) Time Factors

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