BACKGROUND Food allergy (FA) and eosinophilic esophagitis (EE) are increasingly common clinical problems. Dendritic cells (DCs) are key regulators of the sensitization and effector phases of allergic immune responses, but their role in these diseases is largely unknown. OBJECTIVE To evaluate for alterations in the phenotype and function of DCs in children with IgE-mediated milk allergy or EE compared to their non-affected siblings. METHODS Plasmacytoid (pDCs) and monocytoid (mDCs) DCs were prepared from peripheral blood of children with milk allergy (FA), EE, and nonaffected siblings (CON). Purified pDCs and mDCs were cultured alone or with autologous CD4+ lymphocytes. Cytokine levels in plasma, or culture supernatants following stimulation, were measured using multiplex array immunoassay. Cell-surface molecule expression was determined by flow cytometry. RESULTS DCs from FA subjects produced greater levels of pro-inflammatory cytokines (IL-6, TNF-α), GM-CSF, and mDC-derived IL-10 compared to controls following allergen exposure. TH2 but not TH1 cytokines were spontaneously produced in DC-CD4+ T cell co-cultures from children with FA and were not significantly increased after stimulation with milk extract, suggesting an ongoing activation in vivo. This hypothesis was further supported by evidence for elevated IL-5 and IL-13 protein in the plasma of children with both FA and EE. The only significant DC phenotypic differences were: 1) reduced levels of CD80 in EE subjects and 2) FcεRI expression that correlated with serum IgE levels in both groups of subjects. CONCLUSION This study suggests that DCs from children with FA and EE produce more pro-inflammatory cytokines, and that their CD4+ T cells are spontaneously activated to produce TH2 cytokines in the presence of FcεRI-bearing DCs.

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