| First Author | Peng B | Year | 2010 |
| Journal | Proc Natl Acad Sci U S A | Volume | 107 |
| Issue | 34 | Pages | 15193-8 |
| PubMed ID | 20696914 | Mgi Jnum | J:163686 |
| Mgi Id | MGI:4829429 | Doi | 10.1073/pnas.1005533107 |
| Citation | Peng B, et al. (2010) Defective feedback regulation of NF-kappaB underlies Sjogren's syndrome in mice with mutated kappaB enhancers of the IkappaBalpha promoter. Proc Natl Acad Sci U S A 107(34):15193-8 |
| abstractText | Feedback regulation of transcription factor NF-kappaB by its inhibitor IkappaBalpha plays an essential role in control of NF-kappaB activity. To understand the biological significance of IkappaBalpha-mediated feedback regulation of NF-kappaB, we generated mice harboring mutated kappaB enhancers in the promoter of the IkappaBalpha gene (IkappaBalpha(M/M)) to inhibit NF-kappaB-regulated IkappaBalpha expression. Here, we report that these mutant mice are defective in NF-kappaB-induced expression of IkappaBalpha. This defective feedback regulation of NF-kappaB by IkappaBalpha not only altered activity of NF-kappaB, but also the expression of NF-kappaB-regulated genes. As a result, IkappaBalpha(M/M), the homozygous knock-in mice with mutated kappaB enhancers in the IkappaBalpha promoter, acquire shorten life span, hypersensitivity to septic shock, abnormal T-cell development and activation, and Sjogren's Syndrome. These findings therefore demonstrate that the IkappaBalpha-mediated feedback regulation of NF-kappaB has an essential role in controlling T-cell development and functions, provide mechanistic insight into the development of Sjogren's Syndrome, and suggest the potential of NF-kappaB signaling as a therapeutic target for Sjogren's Syndrome and other autoimmune diseases. |
