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  • Title: Reduced IFN-γ receptor expression and attenuated IFN-γ response by dendritic cells in patients with atopic dermatitis.
    Author: Gros E, Petzold S, Maintz L, Bieber T, Novak N.
    Journal: J Allergy Clin Immunol; 2011 Nov; 128(5):1015-21. PubMed ID: 21774972.
    Abstract:
    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-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. 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-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. CONCLUSION: 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.
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