Roles of T_H1 and T_H2 cytokines in a murine model of allergic dermatitis

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Abstract

Skin lesions in atopic dermatitis (AD) are characterized by hypertrophy of the dermis and epidermis, infiltration by T cells and eosinophils, and expression of the cytokines IL-4, IL-5, and IFN-γ. The role of these cytokines in the pathogenesis of AD is not known. We took advantage of a recently described murine model of AD elicited by epicutaneous sensitization with ovalbumin (OVA) (1) and of the availability of mice with targeted deletions of the IL-4, IL-5, and IFN-γ cytokine genes to assess the role of these cytokines in this model.OVA-sensitized skin from IL-5–/– mice had no detectable eosinophils and exhibited decreased epidermal and dermal thickening. Sensitized skin from IL-4–/– mice displayed normal thickening of the skin layers but had a drastic reduction in eosinophils and a significant increase in infiltrating T cells. These findings were associated with a reduction in eotaxin mRNA and an increase in mRNA for the T-cell chemokines macrophage inflammatory protein-2 (MIP-2), MIP-1β, and RANTES. Sensitized skin from IFN-γ–/– mice was characterized by reduced dermal thickening.These results suggest that both the TH2 cytokines IL-4 and IL-5 and the TH1 cytokine IFN-γ play important roles in the inflammation and hypertrophy of the skin in AD.

Authors

Jonathan M. Spergel, Emiko Mizoguchi, Hans Oettgen, Atul K. Bhan, Raif S. Geha