Reduced IFN-γ receptor expression and attenuated IFN-γ response by dendritic cells in patients with atopic dermatitis.

Abstract

Atopic dermatitis (AD) is characterized by a predominance of T(H)2 immune reactions but weaker T(H)1 immune responses in acute skin lesions. To evaluate whether enhanced T(H)2 immunity in patients with AD might impair T(H)1 immune responses by affecting the IFN-γ responsiveness of antigen-presenting cells, we investigated IFN-γ receptor and IL-4 receptor α chain expression, IFN-γ signaling, and the expression of IFN-γ-responsive mediators in dendritic cells (DCs) and their precursors from patients with AD compared with those from healthy subjects. Skin biopsy specimens were obtained and both monocytes and monocyte-derived dendritic cells (MoDCs) from patients with AD (n = 86) and control subjects (n = 84) were analyzed by means of flow cytometry, real-time PCR, ELISA, and HPLC. We observed lower IFN-γ receptor II expression combined with higher IL-4 receptor α chain expression on epidermal DCs, monocytes, and MoDCs from patients with AD. Induction of IFN-γ-inducible factors, such as interferon regulatory factor 1, interferon-inducible protein 10, and indoleamine 2,3-dioxygenase, was attenuated in IFN-γ-pulsed MoDCs from patients with AD. Weaker signal transducer and activator of transcription 1 activation mirrored by lower phosphorylated signal transducer and activator of transcription 1 levels in response to IFN-γ stimulation could be observed in epidermal DCs, monocytes, and MoDCs from patients with AD. Impaired IFN-γ signaling together with attenuated IFN-γ responses in DCs and their precursor cells might contribute to the T(H)2 bias in patients with AD.