| Autor: |
Shih VF; Signaling Systems Laboratory, Department of Chemistry and Biochemistry and San Diego Center for Systems Biology, University of California, San Diego, La Jolla, California, USA., Davis-Turak J, Macal M, Huang JQ, Ponomarenko J, Kearns JD, Yu T, Fagerlund R, Asagiri M, Zuniga EI, Hoffmann A |
| Jazyk: |
angličtina |
| Zdroj: |
Nature immunology [Nat Immunol] 2012 Dec; Vol. 13 (12), pp. 1162-70. Date of Electronic Publication: 2012 Oct 21. |
| DOI: |
10.1038/ni.2446 |
| Abstrakt: |
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 IκBɛ. 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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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