Mast cells regulate IFN-γ expression in the skin and circulating IgE levels in allergen-induced skin inflammation

Abstract

Background: Mast cells are important effector cells in IgE-mediated allergic reactions. They are present in normal skin and increased in skin lesions of patients with atopic dermatitis (AD). Objective: We used mice deficient in mast cells (W/Wv) to assess the role of these cells in a murine model of allergen-induced skin inflammation induced by repeated epicutaneous sensitization with ovalbumin (OVA); the model exhibits many of the characteristics of AD. Methods: Mice deficient in mast cells were sensitized with OVA. Histologic and immunohistochemical examinations, as well as measurements of IL-4 and IFN-γ mRNA, were performed on OVA-sensitized skin. Total and antigen-specific serum IgE levels were determined. Results: Infiltration in W/Wv mice by mononuclear cells, T cells, and eosinophils in OVA-sensitized skin was comparable to that in wild-type (WT) controls. Expression of IL-4 mRNA in sensitized skin sites was similarly increased in WT and W/Wv mice. However, IFN-γ mRNA expression was significantly increased in sensitized skin of W/Wv mice but not in that of WT controls. IL-4 mRNA was readily detectable in unsensitized skin of WT controls but not in that of W/W,v mice, whereas expression of IL-12 p40 mRNA was significantly increased in unsensitized skin of W/Wv mice in comparison with WT controls. Total serum IgE levels were significantly increased after epicutaneous sensitization in W/Wv mice in comparison with WT controls. Conclusion: These results suggest that mast cells regulate IFN-γ expression in the skin and IgE levels in the circulation in a model of allergen-induced skin inflammation with similarities to AD. This is important, given the role of IFN-γ in keratinocyte injury in AD and the role of IgE-mediated reactions in exacerbating AD.