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 T(H)1 responses. However, distinct subsets of DCs have also been shown to induce T(H)2 differentiation.

Objective: We hypothesized that DCs from atopic and nonatopic individuals might differ in their propensity to skew T-cell responses to either the T(H)1 type or the T(H)2 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 T(H)2-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 T(H)1 outcome in the patient and thus to the disease.