Journal
JOURNAL OF IMMUNOLOGY
Volume 178, Issue 11, Pages 6777-6788Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.178.11.6777
Keywords
-
Categories
Funding
- NIAID NIH HHS [R01 AI059715] Funding Source: Medline
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI059715] Funding Source: NIH RePORTER
Ask authors/readers for more resources
TLRs play a critical role in inducing inflammatory and immune responses against microbial agents. In this study, we have investigated the role of NF-kappa B transcription factors in regulating TLR-induced gene expression in dendritic cells, a key APC type. The p50 and cRel NF-kappa B subunits were found to be crucial for regulating genes important for dendritic cell-induced T cell responses (e.g., CD40, IL-12, and IL-18) but not for genes encoding inflammatory cytokines (e.g., TNF-alpha, IL-1 alpha, and IL-6). In striking contrast, the RelA subunit was crucial for expression of inflammatory cytokine genes but not T cell stimulatory genes. These novel findings reveal a fundamentally important difference in biological function of genes regulated by different NF-kappa B subunits. Focusing on RelA target gene specificity mechanisms, we investigated whether the kappa B site and/or the unique composition of RelA played the most crucial role. Surprisingly, studies of IL-6 expression showed that the kappa B site is not a primary determinant of RelA target gene specificity. Instead, a major specificity mechanism is the unique ability of RelA to interact with the transcriptional coactivator CREB-binding protein, a function not shared with the closely related cRel subunit. Together, our findings indicate novel and critically important overall roles of NF-kappa B in TLR-induced gene expression that are mediated by unique functions of distinct subunits.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available