Engagement of the Fc epsilon RI stimulates the production of IL-16 in Langerhans cell-like dendritic cells

Preferential uptake and presentation of IgE-bound allergens by epidermal La ngerhans cells (LC) via the high affinity IgE receptor, Fe epsilon RI, is r egarded as an important mechanism in the induction of cutaneous inflammatio n in atopic dermatitis. Here, we show that activation of monocyte-derived L C-like dendritic cells (LLDC) through engagement of Fc epsilon RI induces t he expression of IL-16, a chemoattractant factor for dendritic cells, CD4() T cells, and eosinophils. We found that ligation of Fc epsilon RI on LLDC derived from atopic dermatitis patients that express high levels of FC eps ilon RI increases IL-16 mRNA expression and storage of intracellular IL-16 protein and enhances the secretion of mature IL-16 in a biphasic manner. An early release of IL-16 (peak at 4 h) is independent of protein synthesis, while a more delayed release (peak at 12 h) requires protein synthesis and occurs subsequent to the induction of IL-16 mRNA and intracellular accumula tion of pro-IL-16. There was evidence that LLDC use caspase-1 to process IL -16, as inhibition of caspase-1, but not of caspase-3, partially prevented the release of IL-16 in response to ligation of Fc epsilon RI. In an in viv o model of IgE-dependent LC activation, the atopy patch test, positive skin reactions were also associated with the induction of IL-16 in epidermal de ndritic cells. These data indicate that IL-16 released from LC. after aller gen-mediated activation through Fc epsilon RI may link IgE-driven and cellu lar inflammatory responses in diseases such as atopic dermatitis.