Jaeschke Anja, Rincón Mercedes, Doran Beth, Reilly Judith, Neuberg Donna, Greiner Dale L, Shultz Leonard D, Rossini Aldo A, Flavell Richard A, Davis Roger J
Howard Hughes Medical Institute and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Proc Natl Acad Sci U S A. 2005 May 10;102(19):6931-5. doi: 10.1073/pnas.0502143102. Epub 2005 May 2.
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.
c-Jun氨基末端激酶亚型（JNK）1与2型糖尿病有关。然而，JNK2蛋白激酶在糖尿病中的潜在作用尚未确定。在此，我们证明JNK2可能在由β细胞自身免疫性破坏引起的1型（胰岛素依赖型）糖尿病中起重要作用。对非肥胖糖尿病小鼠的研究表明，Mapk9基因（编码JNK2蛋白激酶）的破坏减少了破坏性胰岛炎，并减缓了疾病向糖尿病的进展。来自JNK2缺陷型非肥胖糖尿病小鼠的CD4(+) T细胞产生的IFN-γ较少，但IL-4和IL-5的量显著增加，表明向Th2表型极化。JNK2在控制免疫反应的Th1/Th2平衡中的这一作用代表了一种针对自身免疫性糖尿病的保护机制。我们得出结论，JNK蛋白激酶可能在糖尿病中起重要作用，包括JNK1在2型糖尿病中的作用以及JNK2在1型糖尿病中的作用。
