%0 Journal Article
%T The p50 Subunit of NF-¦ÊB Orchestrates Dendritic Cell Lifespan and Activation of Adaptive Immunity
%A Paola Larghi
%A Chiara Porta
%A Elena Riboldi
%A Maria Grazia Totaro
%A Lorenzo Carraro
%A Ciriana Orabona
%A Antonio Sica
%J PLOS ONE
%D 2012
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0045279
%X 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-¦ÊB, 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-¦Â, 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-¦ÊB 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.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0045279