Essential roles of c-Rel in TLR-induced IL-23 p19 gene expression in dendritic cells

Carmody, R. J. , Ruan, Q., Liou, H.-C. and Chen, Y. H. (2007) Essential roles of c-Rel in TLR-induced IL-23 p19 gene expression in dendritic cells. Journal of Immunology, 178(1), pp. 186-91.

Abstract

IL-23 plays crucial roles in both immunity against pathogens and autoimmunity against self. Although it is well recognized that IL-23 expression is restricted to the myeloid lineage and is tightly regulated at the transcriptional level, the nature of transcription factors required for IL-23 expression is poorly understood. We report, in this study, that murine dendritic cells deficient in c-Rel, a member of the NF-kappaB family, are severely compromised in their ability to transcribe the p19 gene, one of the two genes that encode the IL-23 protein. The p19 gene promoter contains three putative NF-kappaB binding sites, two of which can effectively bind c-Rel as determined by chromatin immunoprecipitation and EMSA. Unexpectedly, mutation of either of these two c-Rel binding sites completely abolished the p19 promoter activity induced by five TLRs (2, 3, 4, 6, and 9) and four members of the NF-kappaB family (c-Rel, p65, p100, and p105). Based on these observations, we conclude that c-Rel controls IL-23 p19 gene expression through two kappaB sites in the p19 promoter, and propose a c-Rel-dependent enhanceosome model for p19 gene activation.

• Item Type: Articles
• Additional Information: This work was supported by National Institutes of Health Grants AI50059, AI055934, and AI55934
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Carmody, Dr Ruaidhri
• Authors: Carmody, R. J., Ruan, Q., Liou, H.-C., and Chen, Y. H.
• Subjects: Q Science > Q Science (General)
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Journal of Immunology
• Publisher: American Association of Immunologists
• ISSN: 0022-1767
• ISSN (Online): 1550-6606