Carsten Gutgesell

Engagement of the FcεRI Stimulates the Production of IL-16 in Langerhans Cell-Like Dendritic Cells

Preferential uptake and presentation of IgE-bound allergens by epidermal Langerhans cells (LC) via the high affinity IgE receptor, FcεRI, is regarded as an important mechanism in the induction of cutaneous inflammation in atopic dermatitis. Here, we show that activation of monocyte-derived LC-like dendritic cells (LLDC) through engagement of FcεRI induces the expression of IL-16, a chemoattractant factor for dendritic cells, CD4+ T cells, and eosinophils. We found that ligation of FcεRI on LLDC derived from atopic dermatitis patients that express high levels of FcεRI 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 accumulation 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 FcεRI. In an in vivo model of IgE-dependent LC activation, the atopy patch test, positive skin reactions were also associated with the induction of IL-16 in epidermal dendritic cells. These data indicate that IL-16 released from LC after allergen-mediated activation through FcεRI may link IgE-driven and cellular inflammatory responses in diseases such as atopic dermatitis.

IL-10 secretion of allergen-specific skin-derived T cells correlates positively with that of the Th2 cytokines IL-4 and IL-5.

Abstract In atopic individuals, allergen‐specific CD4+ T lymphocytes often belong to the T‐helper 2 (Th2) subset as they secrete the marker cylokincs interleukin‐4 (IL‐4) and IL‐5 but not intcrfcron‐y (INF‐y). IL‐10 is a cytokine the production of which, in the mouse system has been described to be restricted to the Th2 subset, but in the human was found to be produced by both ThI and Th2 T cell clones (TCC). We have recently shown that house dust mite antigen (Dermatophagoides pteron‐yssinus)‐specific TCC isolated from skin of patients with atopic dermatitis have a more polarized Th2 cytokine production profile than TCC obtained from the peripheral blood of these patients. In this study, we report that skin‐derived TCC secrete more IL‐10, IL‐4 and IL‐5, than TCC isolated from the blood of the same individual (p < 0.05). The difference was more significant with specific TCC than with non‐specific TCC. Furthermore, there was a positive correlation between the production of IL‐10 and that of IL‐4 and IL‐5, respectively. In addition, the amount of IL‐4 and IL‐5 secreted by specific TCC from the skin correlated positively. These results were confirmed by the detection of mRNA by PCR. Finally, our data confirm that in human blood‐derived TCC IL‐10 secretion is not related to a particular cytokine production profile. We suggest that the skin of AD provides an unique environment for the development of aTh2‐likc secretion pattern not only with respect to IL‐4 and IL‐5 but also regarding IL‐10.

Natural Rubber Latex Allergy Is Not a Cause of Sudden Infant Death

Background: The causes for sudden infant death (SID) remain unclear. As infants can become sensitized to NRL allergens by pacifiers and latex mattresses, we tried to establish whether there is a relationship between SID and natural rubber latex (NRL) allergy. Methods: We determined NRL–specific IgE concentrations in 112 unselected cases of SID by the CAP–FEIA method. Results: NRL–specific IgE could be detected only in 1 sample (0.64 kU/l; CAP class 1). Conclusions: We conclude that NRL allergy is not a cause of SID.