title: Sensitization via healthy skin programs Th2 responses in individuals with atopic dermatitis.
abstract: Allergen-specific responses in atopic dermatitis (AD) are skewed toward a Th2 profile. However, individuals with AD have been shown to make effective virus-specific Th1 responses, raising the possibility that the skin itself contributes to driving the AD Th2 immunophenotype. Therefore, to explore the programming of immunological sensitization by the skin, we examined the outcome of sensitization through non-lesional skin of individuals with AD and healthy controls. Volunteers (controls, AD individuals with filaggrin gene (FLG) mutations (ADFM), and AD individuals without FLG mutations (ADWT)) were sensitized by cutaneous application of 2,4-dinitrochlorobenzene (DNCB), a small, highly lipophilic chemical sensitizer. At the doses tested, DNCB showed equal penetration into skin of all groups. Clinical reactions to DNCB were significantly reduced in AD. Although both controls and AD made systemic DNCB-specific Th1 responses, these were reduced in AD and associated with significantly Th2-skewed DNCB-specific T-cell responses. Th2 skewing was seen in both ADFM and ADWT, with no difference between these groups. After 3 months, DNCB-specific Th2 responses were persistent in individuals with AD, and Th1 responses persisted in controls. These data provide evidence that when antigen penetration is not limiting, AD skin has a specific propensity to Th2 programming, suggesting the existence of altered skin immune signaling that is AD-specific and independent of FLG status.
authors.affiliation: Sir Henry Wellcome Laboratories, Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK.
authors.forename: Louise
authors.initials: L
authors.lastname: Newell
authors.affiliation: Sir Henry Wellcome Laboratories, Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK.
authors.forename: Marta E
authors.initials: ME
authors.lastname: Polak
authors.affiliation: Sir Henry Wellcome Laboratories, Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK.
authors.forename: Jay
authors.initials: J
authors.lastname: Perera
authors.affiliation: Sir Henry Wellcome Laboratories, Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Owen
authors.affiliation: Sir Henry Wellcome Laboratories, Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Boyd
authors.affiliation: Sir Henry Wellcome Laboratories, Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK.
authors.forename: Christopher
authors.initials: C
authors.lastname: Pickard
authors.affiliation: Sir Henry Wellcome Laboratories, Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Howarth
authors.affiliation: Sir Henry Wellcome Laboratories, Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK.
authors.forename: Eugene
authors.initials: E
authors.lastname: Healy
authors.affiliation: Sir Henry Wellcome Laboratories, Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK; Human Genetics and Medical Genomics, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK.
authors.forename: John W
authors.initials: JW
authors.lastname: Holloway
authors.affiliation: Sir Henry Wellcome Laboratories, Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Friedmann
authors.affiliation: Sir Henry Wellcome Laboratories, Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK. Electronic address: m.aj@soton.ac.uk.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Ardern-Jones
mesh_terms: D000328:Adult; D000485:Allergens / Q000276:immunology; D002478:Cells, Cultured; D017449:Dermatitis, Allergic Contact / Q000235:genetics / Q000276:immunology*; D003876:Dermatitis, Atopic / Q000139:chemically induced / Q000235:genetics / Q000276:immunology*; D004137:Dinitrochlorobenzene / Q000008:administration & dosage / Q000493:pharmacokinetics; D005260:Female; D000091344:Filaggrin Proteins; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D016130:Immunophenotyping; D007381:Intermediate Filament Proteins / Q000235:genetics; D007509:Irritants / Q000008:administration & dosage / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D012867:Skin / Q000166:cytology / Q000276:immunology*; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology*; D055815:Young Adult
chemical_list: D000485:Allergens; D004137:Dinitrochlorobenzene; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D007509:Irritants