%0 Journal Article %T NF-{kappa}B is required for STAT-4 expression during dendritic cell maturation. %+ Signalisation des Cytokines - Cytokine Signaling %+ Department of Infectious, Parasitic and Immune-Mediated Diseases [Rome] %A Pellegrini, Sandra %A Remoli, M.E. %A Ragimbeau, Josiane %A Giacomini, E. %A Gafa, V. %A Severa, M. %A Lande, R. %A Coccia, E.M. %< avec comité de lecture %@ 0741-5400 %J Journal of Leukocyte Biology %I Society for Leukocyte Biology %V 81(1) %P 355-63 %8 2007-01-01 %D 2007 %R 10.1189/jlb.0506319 %M 17046972 %Z Life Sciences [q-bio]/ImmunologyJournal articles %X The transcription factor STAT-4 plays a pivotal role in the IL-12-mediated development of naive CD4+ T cells into the Th1 phenotype. Initially thought to be restricted to the lymphoid lineage, STAT-4 was subsequently shown to be expressed in the myeloid compartment, mainly in activated monocytes, macrophages, and dendritic cells (DC). Here, we have studied STAT-4 in human monocyte-derived DC, and we demonstrated that its expression can be induced by multiple stimuli, such as the ligands for TLR-4, TLR-2, and TLR-3, different pathogens, CD40 ligand, and the proinflammatory cytokines TNF-alpha and IL-1beta. It is interesting that we found that STAT-4 is tyrosine-phosphorylated in response to type I IFN but not IL-12 in human mature DC. Cloning and functional analysis of the STAT-4 promoter showed that a NF-kappaB binding site, localized at -969/-959 bp upstream of the transcriptional start site, is involved in the regulation of this gene in primary human DC. EMSAs using a probe containing this NF-kappaB binding sequence and chromatin immunoprecipitation indicated that p65/p50 and p50/p50 dimers were the main NF-kappaB/Rel proteins involved in STAT-4 gene expression in maturing DC. The mutation of this kappaB site or the overexpression of the repressor IkappaBalpha exerted an inhibitory effect on a STAT-4 promoter-driven reporter as well as on STAT-4 expression. Altogether, these results indicate that STAT-4 can be finely tuned along with DC maturation through NF-kappaB activation and that its induction may be involved in preparing the DC to be receptive to the cytokine environment present in lymphoid organs. %G English %L pasteur-00161345 %U https://pasteur.hal.science/pasteur-00161345 %~ PASTEUR %~ RIIP_PARIS %~ TEST3-HALCNRS