| First Author | Wang X | Year | 2014 |
| Journal | J Immunol | Volume | 193 |
| Issue | 5 | Pages | 2538-45 |
| PubMed ID | 25057006 | Mgi Jnum | J:319122 |
| Mgi Id | MGI:6862797 | Doi | 10.4049/jimmunol.1400675 |
| Citation | Wang X, et al. (2014) Differential requirement for the IKKbeta/NF-kappaB signaling module in regulating TLR- versus RLR-induced type 1 IFN expression in dendritic cells. J Immunol 193(5):2538-45 |
| abstractText | Host innate-immune responses are tailored by cell type to control and eradicate specific infectious agents. For example, an acute RNA virus infection can result in high-level expression of type 1 IFNs by both conventional dendritic cells (cDCs) and plasmacytoid dendritic cells (pDCs), but whereas cDCs preferentially use RIG-I-like receptor (RLR) signaling to produce type 1 IFNs, pDCs predominantly use TLRs to induce these cytokines. We previously found that the IkappaB kinase beta (IKKbeta)/NF-kappaB pathway regulates early IFN-beta expression, but not the magnitude of type 1 IFN expression following RLR engagement. In this study, we use IKKbeta inhibition and mice deficient in IKKbeta or canonical NF-kappaB subunits (p50, RelA/p65, and cRel) to demonstrate that the IKKbeta/NF-kappaB axis is critical for virus-induced type 1 IFN expression in pDCs, but not in cDCs. We also reveal a crucial and more general requirement for IKKbeta/NF-kappaB in TLR- but not RLR-induced expression of type 1 IFNs and inflammatory cytokines. Together, these findings reveal a previously unappreciated specificity of the IKKbeta/NF-kappaB signaling axis in regulation of antimicrobial responses by different classes of pattern recognition receptors, and therefore by individual cell types reliant on particular pattern recognition receptors for their innate-immune transcriptional responses. |
