Langerhans cell?like dendritic cells and inflammatory dendritic epidermal cell?like dendritic cells induce distinct T-cell responses

Abstract

Allergic reactions are driven by the continuous flow of antigen uptake and presentation processes, which are perpetuated mainly by dendritic cells (DCs). Atopic dermatitis (AD) is a biphasic inflammatory skin disease characterized by an initial phase predominated by TH2 cytokines that switches to a second and more chronic TH1-dominated eczematous phase. However, cellular and soluble factors initiating this switch have not been elucidated thus far. In this issue of the Journal, Novak et al (p 949) show with the help of a novel in vitro model that Langerhans cell–like DCs (LC-DCs) and inflammatory dendritic epidermal cell–like DCs (IDEC-DCs) activated via the high affinity receptor for IgE (FcεRI) contribute distinctly to the outcome of T-cell responses in vitro and might therefore have implications on the biphasic nature of AD in vivo. FcεRI-activated LC-DCs release signals that contribute to the recruitment of precursor cells of IDEC-DCs and the induction of an immune response of the TH2 type. In contrast, FcεRI-activated IDEC-DCs produce high amounts of proinflammatory cytokines and chemokines and might amplify the inflammatory immune reaction in the skin of patients with AD in this way. FcεRI-activated IDEC-DCs prime naive T cells into IFN-γ–producing T cells of the TH1 type (see illustration) and release IL-12 and IL-18, which together might lead to the switch of the initial TH2 into an immune response of the TH1 type in AD in vivo. Allergic reactions are driven by the continuous flow of antigen uptake and presentation processes, which are perpetuated mainly by dendritic cells (DCs). Atopic dermatitis (AD) is a biphasic inflammatory skin disease characterized by an initial phase predominated by TH2 cytokines that switches to a second and more chronic TH1-dominated eczematous phase. However, cellular and soluble factors initiating this switch have not been elucidated thus far. In this issue of the Journal, Novak et al (p 949) show with the help of a novel in vitro model that Langerhans cell–like DCs (LC-DCs) and inflammatory dendritic epidermal cell–like DCs (IDEC-DCs) activated via the high affinity receptor for IgE (FcεRI) contribute distinctly to the outcome of T-cell responses in vitro and might therefore have implications on the biphasic nature of AD in vivo. FcεRI-activated LC-DCs release signals that contribute to the recruitment of precursor cells of IDEC-DCs and the induction of an immune response of the TH2 type. In contrast, FcεRI-activated IDEC-DCs produce high amounts of proinflammatory cytokines and chemokines and might amplify the inflammatory immune reaction in the skin of patients with AD in this way. FcεRI-activated IDEC-DCs prime naive T cells into IFN-γ–producing T cells of the TH1 type (see illustration) and release IL-12 and IL-18, which together might lead to the switch of the initial TH2 into an immune response of the TH1 type in AD in vivo.