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-beta, 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(H)1 and T(H)2 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(H)1 cells, IFN-gamma, or TNF-alpha.


CONCLUSIONS
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.
Verhagen
Johan
J
Swiss Institute of Allergy and Asthma Research, Davos Platz, Switzerland.
Akdis
Mübeccel
M
Traidl-Hoffmann
Claudia
C
Schmid-Grendelmeier
Peter
P
Hijnen
Dirkjan
D
Knol
Edward F
EF
Behrendt
Heidrun
H
Blaser
Kurt
K
Akdis
Cezmi A
CA
D000328:Adult; D017209:Apoptosis; D003876:Dermatitis, Atopic / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000032:analysis / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology; D008875:Middle Aged; D018123:Receptors, Interleukin / Q000032:analysis; D053701:Receptors, Interleukin-10; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis; D012867:Skin / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000032:analysis
D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma