| First Author | Shih VF | Year | 2012 |
| Journal | Nat Immunol | Volume | 13 |
| Issue | 12 | Pages | 1162-70 |
| PubMed ID | 23086447 | Mgi Jnum | J:190685 |
| Mgi Id | MGI:5449469 | Doi | 10.1038/ni.2446 |
| Citation | Shih VF, et al. (2012) Control of RelB during dendritic cell activation integrates canonical and noncanonical NF-kappaB pathways. Nat Immunol 13(12):1162-70 |
| abstractText | The NF-kappaB protein RelB controls dendritic cell (DC) maturation and may be targeted therapeutically to manipulate T cell responses in disease. Here we report that RelB promoted DC activation not as the expected RelB-p52 effector of the noncanonical NF-kappaB pathway, but as a RelB-p50 dimer regulated by canonical IkappaBs, IkappaBalpha and IkappaBvarepsilon. IkappaB control of RelB minimized spontaneous maturation but enabled rapid pathogen-responsive maturation. Computational modeling of the NF-kappaB signaling module identified control points of this unexpected cell type-specific regulation. Fibroblasts that we engineered accordingly showed DC-like RelB control. Canonical pathway control of RelB regulated pathogen-responsive gene expression programs. This work illustrates the potential utility of systems analyses in guiding the development of combination therapeutics for modulating DC-dependent T cell responses. |
