title: Human Atopic Dermatitis Skin-derived T Cells can Induce a Reaction in Mouse Keratinocytes in vivo.
abstract: In atopic dermatitis (AD), the inflammatory response between skin-infiltrating T cells and keratinocytes is fundamental to the development of chronic lesional eczema. The aim of this study was to investigate whether skin-derived T cells from AD patients could induce an inflammatory response in mice through keratinocyte activation and consequently cause the development of eczematous lesions. Punch biopsies of the lesional skin from AD patients were used to establish skin-derived T cell cultures, which were transferred to NOD.Cg-Prkd(scid) Il2rg(tm1Sug) /JicTac (NOG) mice. We found that the subcutaneous injection of the human AD skin-derived T cells resulted in the migration of the human T cells from subcutis to the papillary dermis followed by the development of erythema and oedema in the mouse skin. Furthermore, the human T cells induced a transient proliferative response in the mouse keratinocytes shown as increased numbers of Ki-67(+) keratinocytes and increased epidermal thickness. Out of six established AD skin-derived T cell cultures, two were superior at inducing a skin reaction in the mice, and these cultures were found to contain >10% CCR10(+) T cells compared to <2% for the other cultures. In comparison, blood-derived in vitro-differentiated Th2 cells only induced a weak response in a few of the mice. Thus, we conclude that human AD skin-derived T cells can induce a reaction in the mouse skin through the induction of a proliferative response in the mouse keratinocytes.
authors.affiliation: Department of Dermato-Allergology, Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.|Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.|LEO Pharma A/S, Ballerup, Denmark.
authors.forename: B C
authors.initials: BC
authors.lastname: Martel
authors.affiliation: Department of Dermato-Allergology, Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Blom
authors.affiliation: Department of Dermato-Allergology, Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: B
authors.initials: B
authors.lastname: Dyring-Andersen
authors.affiliation: Department of Dermato-Allergology, Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Skov
authors.affiliation: Department of Dermato-Allergology, Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: K
authors.initials: K
authors.lastname: Thestrup-Pedersen
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: S
authors.initials: S
authors.lastname: Skov
authors.affiliation: LEO Pharma A/S, Ballerup, Denmark.
authors.forename: K
authors.initials: K
authors.lastname: Skak
authors.affiliation: Department of Dermato-Allergology, Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: L K
authors.initials: LK
authors.lastname: Poulsen
mesh_terms: D000328:Adult; D000818:Animals; D016516:CD4-CD8 Ratio; D040501:Calgranulin A / Q000096:biosynthesis; D002465:Cell Movement / Q000276:immunology; D049109:Cell Proliferation; D003876:Dermatitis, Atopic / Q000276:immunology*; D004485:Eczema / Q000276:immunology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D015603:Keratinocytes / Q000276:immunology*; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D012867:Skin / Q000166:cytology / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology* / Q000637:transplantation*; D014183:Transplantation, Heterologous; D055815:Young Adult
chemical_list: D040501:Calgranulin A; D007376:Interleukin-2; D015847:Interleukin-4