FcεRI engagement of Langerhans cell–like dendritic cells and inflammatory dendritic epidermal cell–like dendritic cells induces chemotactic signals and different T-cell phenotypes in vitro

Abstract

Background Atopic dermatitis (AD) is a biphasic inflammatory skin disease characterized by an initial phase predominated by T H2 cytokines, which switches into a second T H1-dominated chronic phase. Thus far, the small number of FcεRI-bearing Langerhans cells (LCs) and inflammatory dendritic epidermal cells (IDECs) in the epidermis of patients with AD has hampered a detailed functional analysis and limited our knowledge of these dendritic cells (DCs). Objective We studied FcεRI-mediated mechanisms of LCs and IDECs with the help of a novel in vitro model. Methods Langerhans cell–like dendritic cells (LC-DCs) and inflammatory dendritic epidermal cell–like dendritic cells (IDEC-DCs) bearing FcεRI have been generated from monocytes of the same atopic donor and compared functionally with LCs and IDECs isolated from the skin of patients with AD. Results We found that FcεRI-activated LC-DCs release chemotactic signals, and supernatants of FcεRI-activated LC-DCs increase the migratory capacity of precursor cells of IDECs and naive T cells in vitro. FcεRI-activated IDEC-DCs produce high amounts of proinflammatory cytokines and chemokines and might thereby amplify the inflammatory immune reaction in patients with AD. Furthermore, FcεRI-activated IDEC-DCs prime naive T cells into IFN-γ–producing T cells and release IL-12 and IL-18, which together might lead to the switch of the initial T H2-type immune response into a response of the T H1 type in vivo. Conclusion The present study provides evidence that FcεRI-activated LC-DCs and IDEC-DCs contribute distinctly to the outcome of T-cell responses in vitro and might have implications for the biphasic nature of AD in vivo.