Staphylococcal exotoxins are strong inducers of IL-22: A potential role in atopic dermatitis

Background: Patients with atopic dermatitis (AD) and psoriasis are frequently colonized with Staphylococcus aureus that produces staphylococcal enterotoxin B (SEB) and alpha-toxin. In patients with AD, S aureus colonization is positively correlated with the severity of their eczema. Moreover, IL-22-producing cells have been shown to accumulate in AD skin and to correlate with disease severity. Objective: To assess IL-22 production in response to SEB and sublytic alpha-toxin stimulation in patients with AD and psoriasis compared with healthy controls. Methods: IL-22 induction was investigated in PBMCs, T cells, and autologous cocultures of keratinocytes and T cells on SEB and alpha-toxin stimulation in a time-dependent and dose-dependent manner at the mRNA and protein (ELISA and flow cytometry) level. Anti-IL-1 receptor or anti-IL-6 antibodies were used in blocking experiments. Results: Staphylococcal enterotoxin B and sublytic alpha-toxin concentrations induced IL-22 production in PBMCs and isolated CD4(+) T cells. IL-22 secretion was enhanced by alpha-toxin stimulation in autologous cocultures of keratinocytes and T cells. In T cells and PBMCs from patients with AD, IL-22 secretion was significantly enhanced on alpha-toxin stimulation compared with patients with psoriasis and healthy controls. Conclusion: Increased IL-22 secretion induced by staphylococcal exotoxins in the skin partially explains how skin colonization and infection with S aureus can contribute to chronic skin inflammation in AD. (J Allergy Clin Immunol 2010;126:1176-83.)