1. The p50 Subunit of NF-κB Orchestrates Dendritic Cell Lifespan and Activation of Adaptive Immunity.
- Author
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Larghi, Paola, Porta, Chiara, Riboldi, Elena, Totaro, Maria Grazia, Carraro, Lorenzo, Orabona, Ciriana, Sica, Antonio, and Hirsch, Emilio
- Subjects
DENDRITIC cells ,IMMUNITY ,IMMUNOLOGICAL tolerance ,IMMUNE response ,APOPTOSIS ,NEUROENDOCRINE tumors ,HOMEOSTASIS - Abstract
Dendritic cells play a central role in keeping the balance between immunity and immune tolerance. A key factor in this equilibrium is the lifespan of DC, as its reduction restrains antigen availability leading to termination of immune responses. Here we show that lipopolysaccharide-driven DC maturation is paralleled by increased nuclear levels of p50 NF-κB, an event associated with DC apoptosis. Lack of p50 in murine DC promoted increased lifespan, enhanced level of maturation associated with increased expression of the proinflammatory cytokines IL-1, IL-18 and IFN-β, enhanced capacity of activating and expanding CD4
+ and CD8+ T cells in vivo and decreased ability to induce differentiation of FoxP3+ regulatory T cells. In agreement, vaccination of melanoma-bearing mice with antigen-pulsed LPS-treated p50-/- BM-DC boosted antitumor immunity and inhibition of tumor growth. We propose that nuclear accumulation of the p50 NF-κB subunit in DC, as occurring during lipopolysaccharide-driven maturation, is a homeostatic mechanism tuning the balance between uncontrolled activation of adaptive immunity and immune tolerance. [ABSTRACT FROM AUTHOR]- Published
- 2012
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