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The p50 subunit of NF-?B orchestrates dendritic cell lifespan and activation of adaptive immunity.


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-?B, 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-?, 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-?B 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.

SUBMITTER: Larghi P 

PROVIDER: S-EPMC3458114 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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The p50 subunit of NF-κB orchestrates dendritic cell lifespan and activation of adaptive immunity.

Larghi Paola P   Porta Chiara C   Riboldi Elena E   Totaro Maria Grazia MG   Carraro Lorenzo L   Orabona Ciriana C   Sica Antonio A  

PloS one 20120925 9


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 in  ...[more]

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