title: Inflammatory conditions distinctively alter immunological functions of Langerhans-like cells and dendritic cells in vitro.
abstract: The specific function of human skin-resident dendritic cell (DC) subsets in the regulation of immunity or tolerance is still a matter of debate. Langerhans cells (LC) induce anti-viral immune responses but, conversely to dermal DC, maintain tolerance to bacteria. However, the definite function of epidermal LC and cutaneous DC appears even more complex under inflammatory conditions. Here we investigated the immune responses of human immature monocyte-derived DC (MoDC) and LC-like cells (MoLC) upon stimulation with different Toll-like receptor ligands in the presence or absence of pro-inflammatory cytokines tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). In MoDC, bacterial antigens selectively up-regulated CD83 and CD86 expression and induced the release of T helper type 1 (Th1) and Th17 cytokines and led to a higher CCR7-dependent migratory capacity compared with a low responsiveness of MoLC. Importantly, MoLC activation with lipopolysaccharide under inflammatory conditions strongly enhanced a phenotypically mature state, increased IL-12p70, IL-23 and IL-6 production and Th1 cytokine secretion by CD4(+) T cells. Treatment with poly(I:C) specifically up-regulated surface expression of co-stimulatory molecules and increased release of IL-12p70 in MoLC and co-stimulation with TNF-α and IL-1β further elevated Th1 and Th17 cytokine production. Poly(I:C)-induced up-regulation of type I interferon mRNA levels in MoLC and MoDC was Toll-like receptor 3-dependent but not, or only weakly, modulated by pro-inflammatory cytokines. Our results indicate that inflammatory conditions greatly facilitate recognition of bacteria by MoLC. Furthermore, we suggest a critical involvement of both subsets in innate defence against viruses, whereas inflammatory skin environments additionally favour MoLC as potent inducers of Th1 and Th17 cytokines.
authors: Institute of Pharmacy (Pharmacology and Toxicology), Freie Universität Berlin, Berlin, Germany.
authors: André
authors: A
authors: Said
authors: Stephanie
authors: S
authors: Bock
authors: Gerrit
authors: G
authors: Müller
authors: Günther
authors: G
authors: Weindl
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis; D051940:B7-2 Antigen / Q000096:biosynthesis; D001424:Bacterial Infections / Q000276:immunology*; D002465:Cell Movement; D002478:Cells, Cultured; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D007249:Inflammation / Q000276:immunology*; D007369:Interferon Inducers / Q000494:pharmacology; D007370:Interferon Type I / Q000235:genetics; D018664:Interleukin-12 / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000494:pharmacology; D053759:Interleukin-23 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D007801:Langerhans Cells / Q000276:immunology*; D008070:Lipopolysaccharides; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D011070:Poly I-C / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D054400:Receptors, CCR7 / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation; D000097802:CD83 Antigen
chemical_list: D015703:Antigens, CD; D051940:B7-2 Antigen; D007136:Immunoglobulins; D007369:Interferon Inducers; D007370:Interferon Type I; D018664:Interleukin-12; D053583:Interleukin-1beta; D053759:Interleukin-23; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011070:Poly I-C; D012333:RNA, Messenger; D054400:Receptors, CCR7; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D000097802:CD83 Antigen; C515370:CCR7 protein, human; C497964:CD86 protein, human; C508585:IL1B protein, human; C508600:IL6 protein, human
keywords: Langerhans cells; Toll-like receptors; dendritic cells; interleukin-1β; tumour necrosis factor-α