Absence of T-regulatory cell expression and function in atopic dermatitis skin

Background: The role of regulatory T cells has been widely reported in the suppression of T-cell activation. A dysfunction in CD4⁺CD25 ⁺ T-regulatory cell-specific transcription factor FoxP3 leads to immune dysregulation, polyendocrinopathy, enteropathy X-linked syndrome, often associated with atopic dermatitis. Increasing the number and activity of regulatory T cells in affected organs has been suggested as a remedy in various inflammatory diseases, including allergy. Objective: To determine the presence and function of regulatory T cells in atopic dermatitis. Methods: Immunohistochemistry of lesional atopic dermatitis skin and control skin conditions was used to demonstrate regulatory cells and cytokines in situ. The role of effector and regulatory T cells as well as their specific cytokines in apoptosis in human keratinocyte cultures and artificial skin equivalents was investigated. Results: Human T-regulatory type 1 cells, their suppressive cytokines, IL-10 and TGF-β, as well as receptors for these cytokines were significantly expressed, whereas CD4⁺CD25⁺FoxP3 ⁺ T-regulatory cells were not found in lesional and atopy patch test atopic dermatitis or psoriasis skin. Both subsets of regulatory T cells suppress the allergen-specific activation of T_H1 and T_H2 cells. In coculture and artificial skin equivalent experiments, subsets of T-regulatory cells neither induced keratinocyte death nor suppressed apoptosis induced by skin T cells, T_H1 cells, IFN-γ, or TNF-α. Conclusion: A dysregulation of disease-causing effector T cells is observed in atopic dermatitis lesions, in association with an impaired CD4⁺CD25 ⁺FoxP3⁺ T-cell infiltration, despite the expression of type 1 regulatory cells in the dermis.