title: Absence of T-regulatory cell expression and function in atopic dermatitis skin.
abstract: 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.
authors.affiliation: Swiss Institute of Allergy and Asthma Research, Davos Platz, Switzerland.
authors.forename: Johan
authors.initials: J
authors.lastname: Verhagen
authors.forename: Mübeccel
authors.initials: M
authors.lastname: Akdis
authors.forename: Claudia
authors.initials: C
authors.lastname: Traidl-Hoffmann
authors.forename: Peter
authors.initials: P
authors.lastname: Schmid-Grendelmeier
authors.forename: Dirkjan
authors.initials: D
authors.lastname: Hijnen
authors.forename: Edward F
authors.initials: EF
authors.lastname: Knol
authors.forename: Heidrun
authors.initials: H
authors.lastname: Behrendt
authors.forename: Kurt
authors.initials: K
authors.lastname: Blaser
authors.forename: Cezmi A
authors.initials: CA
authors.lastname: Akdis
mesh_terms: 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
chemical_list: 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