Control of RelB during dendritic cell activation integrates canonical and noncanonical NF-?B pathways.

ABSTRACT: The NF-?B 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-?B pathway, but as a RelB-p50 dimer regulated by canonical I?Bs, I?B? and I?B?. I?B control of RelB minimized spontaneous maturation but enabled rapid pathogen-responsive maturation. Computational modeling of the NF-?B 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.

SUBMITTER: Shih VF 

PROVIDER: S-EPMC3634611 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature