title: Langerhans cell homeostasis and activation is altered in hyperplastic human papillomavirus type 16 E7 expressing epidermis.
abstract: It has previously been shown that expression of human papillomavirus type 16 (HPV) E7 in epidermis causes hyperplasia and chronic inflammation, characteristics of pre-malignant lesions. Importantly, E7-expressing epidermis is strongly immune suppressed and is not rejected when transplanted onto immune competent mice. Professional antigen presenting cells are considered essential for initiation of the adaptive immune response that results in graft rejection. Langerhans cells (LC) are the only antigen presenting cells located in normal epidermis and altered phenotype and function of these cells may contribute to the immune suppressive microenvironment. Here, we show that LC are atypically activated as a direct result of E7 expression in the epidermis, and independent of the presence of lymphocytes. The number of LC was significantly increased and the LC are functionally impaired, both in migration and in antigen uptake. However when the LC were extracted from K14E7 skin and matured in vitro they were functionally competent to present and cross-present antigen, and to activate T cells. The ability of the LC to present and cross-present antigen following maturation supports retention of full functional capacity when removed from the hyperplastic skin microenvironment. As such, opportunities are afforded for the development of therapies to restore normal LC function in hyperplastic skin.
authors.affiliation: University of Queensland Diamantina Institute, Translational Research Institute, 37 Kent Street, Woolloongabba, Brisbane, Qld 4102, Australia.
authors.forename: Nor Malia
authors.initials: NM
authors.lastname: Abd Warif
authors.affiliation: Department of Dermatology and Venereology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Stoitzner
authors.affiliation: University of Queensland Diamantina Institute, Translational Research Institute, 37 Kent Street, Woolloongabba, Brisbane, Qld 4102, Australia.
authors.forename: Graham R
authors.initials: GR
authors.lastname: Leggatt
authors.affiliation: University of Queensland Diamantina Institute, Translational Research Institute, 37 Kent Street, Woolloongabba, Brisbane, Qld 4102, Australia.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Mattarollo
authors.affiliation: University of Queensland Diamantina Institute, Translational Research Institute, 37 Kent Street, Woolloongabba, Brisbane, Qld 4102, Australia.
authors.forename: Ian H
authors.initials: IH
authors.lastname: Frazer
authors.affiliation: Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: Merilyn H
authors.initials: MH
authors.lastname: Hibma
mesh_terms: D000818:Animals; D002452:Cell Count; D002465:Cell Movement; D002478:Cells, Cultured; D004817:Epidermis / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D006965:Hyperplasia / Q000276:immunology / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D007801:Langerhans Cells / Q000276:immunology / Q000473:pathology*; D051379:Mice; D050725:Papillomavirus E7 Proteins / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D050725:Papillomavirus E7 Proteins; C059731:oncogene protein E7, Human papillomavirus type 16