Food allergy, dermatologic diseases, and anaphylaxis
Absence of T-regulatory cell expression and function in atopic dermatitis skin

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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 TH1 and TH2 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, TH1 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.

Section snippets

Subjects

PBMCs were isolated from peripheral blood of 15 healthy volunteers or patients with AD (aged 19-45 years) hypersensitive to house dust mite (HDM) or birch pollen allergens and then purified or cultured to provide the various types of T cells used in this study.

Twenty-four–hour positive atopy patch test (APT) biopsies were taken of 3 patients with AD at the University Medical Center Utrecht, The Netherlands, as previously described.15 Three psoriasis biopsies were obtained from the ZAUM-Center

Expression of IL-10 and TGF-β as well as their receptors, but not FoxP3, in lesional AD skin

To investigate the expression and function of Treg cells in AD, we looked at whether the Tr1 cell-specific cytokines, IL-10 and TGF-β, or CD4+CD25+ Treg cell-specific transcription factor FoxP3 are expressed in lesional AD skin. Despite the presence of large numbers of CD25+ cells (Fig 1, A), we did not detect any FoxP3+ cells, neither in the dermal infiltrate of chronic lesional AD skin nor in acutely inflamed skin 24 hours after APT, psoriatic skin, or healthy skin (Fig 1, B). FoxP3 was

Discussion

During the last decade, a significant amount of data has accumulated on the suppressive effects of Tr1 or CD4+CD25+ T-regulatory cells in models of autoimmunity, allergy, transplantation tolerance, tumor tolerance, and chronic infections.12, 23 The efficacy of various Treg cell subsets in the suppression of inflammation has tempted scientists to speculate that increasing Treg cell numbers may suppress inflammation and tissue injury in affected organs. In the current study, we show that FoxP3+

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    Authors' laboratories supported by Swiss National Science Foundation grants No. 31-105865 and 32-100266 and the Global Allergy and Asthma European Network (GA2LEN).

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