IL-4 induces the intracellular expression of the α chain of the high-affinity receptor for IgE in in vitro-generated dendritic cells

Background: Recent findings have shown that the surface expression of the high-affinity receptor for IgE (Fc epsilon RI) on human CD1a(+) Langerhans cells (LC) and related dendritic cells (DC) in the skin, despite a constant intracellular expression of its alpha chain (Fc epsilon RI alpha), is highly up-regulated in atopic dermatitis. Moreover, this surface expression correlates with the IgE serum level, strongly suggesting yet-to-be-defined common signals in the regulation of Fc epsilon RI display on LC/DC and IgE synthesis. Objectives: In this study me examined the influence of different cytokines on the expression of Fc epsilon RI on in vitro-generated CD1a(+) LC/DC; Methods: CD34(+) precursor cells were isolated from cord blood with use of high-gradient magnetic cell sorting, cultured with GM-CSF; TNF-alpha, IL-4, or IFN-gamma, and surface and cytoplasmic staining for flow cytometry were performed. Results: IL-4 strongly enhanced the generation of CD1a(+) LC/DC and also up-regulated the expression of the skin-homing structures E-cadherin and cutaneous lymphocyte antigen, In contrast, IFN-gamma was found to suppress the E-cadherin expression and to be a strong antagonist of IL-4 by inhibiting the production of CD1a(+) cells. Most important, IL-4 induced the cytoplasmic expression of Fc epsilon RI alpha in CD1a(+) LC/DC but not its surface expression. This up-regulation was antagonized by IFN-gamma. Conclusion: IL-4 is not only a key cytokine in the regulation of IgE hut also induces the expression of its receptor binding chain as well as up-regulation of skin homing molecules on LC/DC. Expression of these structures during generation of LC/DC reflects the in vivo situation encountered in LC.