RESUMEN
The NF-κB 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-κB pathway, but as a RelB-p50 dimer regulated by canonical IκBs, IκBα and IκBÉ. IκB control of RelB minimized spontaneous maturation but enabled rapid pathogen-responsive maturation. Computational modeling of the NF-κB 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.
Asunto(s)
Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Activación de Linfocitos , FN-kappa B/metabolismo , Factor de Transcripción ReIB/metabolismo , Animales , Diferenciación Celular/genética , Línea Celular , Fibroblastos/metabolismo , Regulación de la Expresión Génica , Quinasa I-kappa B/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , FN-kappa B/genética , Multimerización de Proteína , Transducción de Señal , Receptor Toll-Like 2/metabolismo , Receptor Toll-Like 4/metabolismo , Receptor Toll-Like 9/metabolismo , Factor de Transcripción ReIB/genéticaRESUMEN
Poly(alpha-methylstyrene)-block-poly(4-hydroxystyrene) acts as both a lithographic deep UV photoresist and a self-assembling material, making it ideal for patterning simultaneously by both top-down and bottom-up fabrication methods. Solvent vapor annealing improves the quality of the self-assembled patterns in this material without compromising its ability to function as a photoresist. The choice of solvent used for annealing allows for control of the self-assembled pattern morphology. Annealing in a nonselective solvent (tetrahydrofuran) results in parallel orientation of cylindrical domains, while a selective solvent (acetone) leads to formation of a trapped spherical morphology. Finally, we have self-assembled both cylindrical and spherical phases within lithographically patterned features, demonstrating the ability to precisely control ordering. Observing the time evolution of switching from cylindrical to spherical morphology within these features provides clues to the mechanism of ordering by selective solvent.