Dendritic cells contribute to the development of atopy by an insufficiency in IL-12 production

Abstract

Background: IL-12 is a crucial factor in the development and course of allergic diseases. By virtue of their IL-12 production, dendritic cells (DCs) are potent inducers of TH1 responses. However, distinct subsets of DCs have also been shown to induce TH2 differentiation. Objective: We hypothesized that DCs from atopic and nonatopic individuals might differ in their propensity to skew T-cell responses to either the TH1 type or the TH2 type. To this end, we investigated the cytokine patterns produced by DCs from atopic and nonatopic individuals, and we attempted to clarify whether this could be due to different DC lineages or, alternatively, to different microenvironmental factors. Methods: DCs were generated from lymphocyte-depleted PBMCs from atopic and nonatopic donors and fully matured with monocyte-conditioned medium. Production of IL-4, IL-5, IL-10, IL-12, and IL-13 in response to CD40 ligation was measured with ELISA. DC subsets were identified in PBMCs from freshly drawn blood by 3-color flow cytometry. Results: Compared with DCs from healthy donors, monocyte-derived DCs from atopic patients produced less bioactive IL-12 and IL-10. DC production of IL-4, IL-13, and IL-5 was not detected. Relatively more CD123+ DCs, corresponding to TH2-inducing "DC2s," were found in PBMCs from atopic patients. Conclusion: The data suggest that in addition to the described abnormalities in the patients' T-cell populations, DCs might also critically contribute to the atopic/allergic TH1 outcome in the patient and thus to the disease.