title: CD4+ T cell depletion changes the cytokine environment from a TH1/TH2 response to a TC17-like response in a murine model of atopic dermatitis.
abstract: Atopic dermatitis (AD) is a common inflammatory skin disease often associated with co-morbidities including allergic hypersensitivity. We have studied induced AD-like disease in NC/Nga mice using the hapten FITC. Following FITC-treatment the NC/Nga mice develop AD-like skin lesions in regard to the histopathological and immunological changes. Consistent with AD in humans the number of CD4(+) T cells within the blood and draining lymph nodes increases considerably. To evaluate the contribution of T(H) cells on disease development we examined the effect of CD4 depletion. Following CD4 depletion the mice still develop AD-like skin lesions characterized by e.g. increased epidermal proliferation, hyperkeratosis and cellular infiltrate, however, the underlying immunological mechanisms change. CD4 depletion results in increased IL-17A and IL-22 production, which traditionally are associated with T(H)17 cells. Using confocal microscopy, we demonstrate that epidermal CD8(+) cells are positive for IL-17A, indicating that these cells are T(C)17 cells, the cytotoxic T cell counterpart to T(H)17 cells. In conclusion, we show that NC/Nga mice develop AD-like disease following CD4 depletion. This is mirrored by an increased production of IL-17A, which we suggest are produced by T(C)17 cells. These findings support that CD8(+) T cells can play a role in AD.
authors.affiliation: Disease Pharmacology, Discovery, Leo Pharma, 2750 Ballerup, Denmark. gitte.christensen@leo-pharma.com
authors.forename: Gitte B
authors.initials: GB
authors.lastname: Christensen
authors.forename: Malene
authors.initials: M
authors.lastname: Hvid
authors.forename: Peter H
authors.initials: PH
authors.lastname: Kvist
authors.forename: Bent
authors.initials: B
authors.lastname: Deleuran
authors.forename: Mette
authors.initials: M
authors.lastname: Deleuran
authors.forename: Christian
authors.initials: C
authors.lastname: Vestergaard
authors.forename: Kaare
authors.initials: K
authors.lastname: Kemp
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D003876:Dermatitis, Atopic / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D004817:Epidermis / Q000276:immunology; D005260:Female; D016650:Fluorescein-5-isothiocyanate / Q000494:pharmacology; D006241:Haptens / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D020381:Interleukin-17 / Q000276:immunology*; D007378:Interleukins / Q000276:immunology*; D051379:Mice; D012867:Skin / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D012871:Skin Diseases / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D000097043:Interleukin-22
chemical_list: D016650:Fluorescein-5-isothiocyanate; D006241:Haptens; D020381:Interleukin-17; D007378:Interleukins; D000097043:Interleukin-22