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

Background: 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. Objectives: To evaluate whether enhanced T(H)2 immunity in patients with AD might impair T(H)1 immune responses by affecting the IFN-gamma responsiveness of antigen-presenting cells, we investigated IFN-gamma receptor and IL-4 receptor a chain expression, IFN-gamma signaling, and the expression of IFN-gamma-responsive mediators in dendritic cells (DCs) and their precursors from patients with AD compared with those from healthy subjects. Methods: 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. Results: We observed lower IFN-gamma receptor II expression combined with higher IL-4 receptor alpha chain expression on epidermal DCs, monocytes, and MoDCs from patients with AD. Induction of IFN-gamma-inducible factors, such as interferon regulatory factor 1, interferon-inducible protein 10, and indoleamine 2,3-dioxygenase, was attenuated in IFN-gamma-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-gamma stimulation could be observed in epidermal DCs, monocytes, and MoDCs from patients with AD. Conclusion: Impaired IFN-gamma signaling together with attenuated IFN-gamma responses in DCs and their precursor cells might contribute to the T(H)2 bias in patients with AD. (J Allergy Clin Immunol 2011;128:1015-21.)