title: HPV16 E7 expression in skin induces TSLP secretion, type 2 ILC infiltration and atopic dermatitis-like lesions.
abstract: Atopic dermatitis is a common pruritic and inflammatory skin disorder with unknown etiology. Most commonly occurring during early childhood, atopic dermatitis is associated with eczematous lesions and lichenification, in which the epidermis becomes hypertrophied resulting in thickening of the skin. In this study, we report an atopic dermatitis-like pathophysiology results in a murine model following the expression of the high-risk human papillomavirus (HPV) 16 oncoprotein E7 in keratinocytes under the keratin 14 promoter. We show that HPV16 E7 expression in the skin is associated with skin thickening, acanthosis and light spongiosis. Locally, HPV16 E7-expressing skin secreted high levels of thymic stromal lymphopoietin (TSLP) and contained increased numbers of innate lymphoid cells (ILCs). High levels of circulating immunoglobulin E were associated with increased susceptibility to skin allergy in a model of cutaneous challenge, and to airway bronchiolar inflammation, enhanced airway goblet cell metaplasia and mucus production in a model of atopic march. Surprisingly, skin pathology occurred independently of T cells and mast cells. Thus, our findings suggest that the expression of a single HPV oncogene in the skin can drive the onset of atopic dermatitis-like pathology through the induction of TSLP and type 2 ILC infiltration.
authors.affiliation: The University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute, Brisbane, QLD, Australia.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Bergot
authors.affiliation: The University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute, Brisbane, QLD, Australia.
authors.forename: Nastasia
authors.initials: N
authors.lastname: Monnet
authors.affiliation: The University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute, Brisbane, QLD, Australia.
authors.forename: Son
authors.initials: S
authors.lastname: Le Tran
authors.affiliation: The University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute, Brisbane, QLD, Australia.
authors.forename: Deepak
authors.initials: D
authors.lastname: Mittal
authors.affiliation: The University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute, Brisbane, QLD, Australia.
authors.forename: Jane
authors.initials: J
authors.lastname: Al-Kouba
authors.affiliation: The University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute, Brisbane, QLD, Australia.
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Steptoe
authors.affiliation: Division of Human Immunology, Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, Australia.
authors.forename: Michele A
authors.initials: MA
authors.lastname: Grimbaldeston
authors.affiliation: The University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute, Brisbane, QLD, Australia.
authors.forename: Ian H
authors.initials: IH
authors.lastname: Frazer
authors.affiliation: The University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute, Brisbane, QLD, Australia.
authors.forename: James W
authors.initials: JW
authors.lastname: Wells
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis*; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D004195:Disease Models, Animal; D015870:Gene Expression; D007113:Immunity, Innate; D000067596:Interleukin-33 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D050725:Papillomavirus E7 Proteins / Q000235:genetics*; D010641:Phenotype; D012867:Skin / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; C506535:Il33 protein, mouse; D000067596:Interleukin-33; D007378:Interleukins; C442281:Mydgf protein, mouse; D050725:Papillomavirus E7 Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse