Food allergy, dermatologic diseases, and anaphylaxis
Characterization of FcεRI-bearing CD123+ blood dendritic cell antigen-2+ plasmacytoid dendritic cells in atopic dermatitis

https://doi.org/10.1016/j.jaci.2004.05.038Get rights and content

Abstract

Background

The high-affinity receptor for IgE (FcεRI) on myeloid dendritic cells has been shown to play a major role in atopic dermatitis (AD). Plasmacytoid dendritic cells (pDCs), which are instrumental in the defense of viral infections, are present in reduced amounts in the skin of patients with AD, which is characterized by a high susceptibility to viral infections.

Objective

We explored phenotypical and functional characteristics of pDC in the peripheral blood of patients with AD and healthy individuals.

Methods

Blood dendritic cell antigen-2+CD123+ pDCs were enriched from the peripheral blood of patients with AD and studied in functional assays.

Results

Skin-homing molecules such as cutaneous lymphocyte antigen and L-selectin CD62L were expressed in lower levels on pDCs of patients with AD. pDCs expressed high amounts of IgE-occupied FcεRI. Further, FcεRI aggregation on pDCs impaired the surface expression of MHC I and II, induced the production of IL-10, and enhanced the apoptosis of pDCs. Importantly, FcεRI preactivated pDC produced less IFN-α and IFN-β after stimulation with CpG motifs and enhanced the outcome of immune responses of the TH2 type.

Conclusion

From these data, we conclude that FcεRI-bearing pDCs from patients with AD (1) are different from pDCs of healthy individuals, (2) might be important in the pathophysiology of AD, and (3) contribute to the enhanced susceptibility of patients with AD to viral infections.

Section snippets

Methods

For the section “Reagents,” please see the ancillary material in the Journal's Online Repository at www.mosby.com/jaci.

CD123+BDCA-2+ pDCs in the peripheral blood of patients with AD display different phenotypical characteristics

First, we evaluated phenotypical characteristics of CD123+BDCA-2+ pDCs in the peripheral blood of patients with AD and healthy, nonatopic volunteers in detail by flow cytometry. BDCA-2+CD123+ pDCs freshly isolated from the blood of patients with AD expressed higher amounts of the costimatory molecule CD80 and the MHC I molecule on their cell surface than BDCA-2+CD123+ pDCs of healthy, nonatopic volunteers (Fig 1). In contrast, surface expression of L-selectin CD62L and cutaneous lymphocyte

Discussion

Although it is generally agreed that pDCs are involved in the elicitation of TH2-type immune responses, the exact mechanisms underlying this process have not been elucidated so far.1 Here we show for the first time that CD123+BDCA-2+ pDCs in the peripheral blood of patients with AD express enhanced amounts of the trimeric variant of FcεRI, which, similar to myeloid DCs, consists of the IgE-binding α-chain and the γ-chain dimer and is mostly occupied with IgE molecules.18 In contrast with the

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    Supported by grants from the Deutsche Forschungsgemeinschaft (DFG NO/454-1-1 and DFG NO/454-2-1) and Bonner Forschungsförderung and by the grant Y078GEN of the Austrian Science Fund and the Forschungsgzentrum für Molekulare Medizin project of the Austrian Academy of Science.

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