Epicutaneous superantigen sensitization induces allergic skin inflammation

Abstract

The skin of patients with atopic dermatitis (AD) is frequently colonized with enteroxin-secreting strains of Staphylococcus aureus that exacerbate AD, suggesting that epicutaneous (EC) exposure to superantigens plays a role in the development and/or persistence of TH2-dominated skin inflammation in AD. In this issue of the Journal, Laouini et al (p 981) tested this hypothesis by examining whether repeated EC sensitization of mice with staphylococcal enterotoxin B (SEB) results in allergic skin inflammation and in TH2 skewing of the immune response to the superantigen. The data show that EC sensitization with SEB elicits a local cutaneous inflammatory response characterized by dermal infiltration with eosinophils and mononuclear cells and by increased mRNA expression of the TH2 cytokine IL-4 but not of the TH1 cytokine IFN-γ. EC-sensitized mice mounted a systemic TH2 response to SEB, as evidenced by elevated total and SEB-specific IgG1 and IgE. Although EC sensitization with SEB resulted in selective depletion of SEB-specific TCR Vβ8+ cells from the spleen and sensitized skin, splenocytes from SEB-sensitized mice secreted relatively more IL-4 and less IFN-γ than saline-sensitized controls, consistent with TH2 skewing of the systemic immune response to the superantigen. The results suggest that EC exposure to superantigens via mechanically injured skin leads to a systemic TH2 response that exacerbates allergic skin inflammation in AD.