title: IL-18, but not IL-12, induces production of IFN-γ in the immunosuppressive environment of HPV16 E7 transgenic hyperplastic skin.
abstract: IFN-γ has a central role in the defense against infections and cancer. More recently, however, IFN-γ has also been reported to have immunosuppressive effects in models of autoimmune disease, melanoma, and premalignant skin disease. Although IL-12 and IL-18 are critical inducers of IFN-γ during infection, the mechanisms that induce IFN-γ in an immunosuppressive context are unknown. Previously, we identified a key role for IFN-γ in mediating the suppression of antigen-specific immune responses in a transgenic mouse model of human papillomavirus (HPV)-associated epidermal hyperplasia, driven by the expression of the HPV16 E7 oncoprotein from a keratin 14 promoter (K14E7). We now demonstrate elevated production of IFN-γ, IL-18, and IL-12 by K14E7 transgenic skin compared with nontransgenic skin. IFN-γ in K14E7 transgenic skin was produced predominantly by CD8(+) and CD4(+) T cells, which were present in greater numbers in K14E7 transgenic skin. Production of IFN-γ in K14E7 skin required IL-18 but not IL-12. Our findings show that IL-18 contributes to inducing IFN-γ in an immunosuppressive cutaneous environment caused by viral oncogene-driven hyperplasia.
authors.affiliation: The University of Queensland Diamantina Institute, Translational Research Institute, Woolloongabba, Brisbane, Queensland, Australia.
authors.forename: Christina
authors.initials: C
authors.lastname: Gosmann
authors.affiliation: The University of Queensland Diamantina Institute, Translational Research Institute, Woolloongabba, Brisbane, Queensland, Australia.
authors.forename: Ian H
authors.initials: IH
authors.lastname: Frazer
authors.affiliation: The University of Queensland Diamantina Institute, Translational Research Institute, Woolloongabba, Brisbane, Queensland, Australia.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Mattarollo
authors.affiliation: The University of Queensland Diamantina Institute, Translational Research Institute, Woolloongabba, Brisbane, Queensland, Australia.
authors.forename: Antje
authors.initials: A
authors.lastname: Blumenthal
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D052162:Human papillomavirus 16 / Q000235:genetics / Q000378:metabolism; D006965:Hyperplasia / Q000378:metabolism / Q000473:pathology; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000378:metabolism*; D018664:Interleukin-12 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020382:Interleukin-18 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D053547:Keratin-14 / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism* / Q000473:pathology*; D017193:Skin Diseases, Viral / Q000378:metabolism* / Q000473:pathology
chemical_list: D020382:Interleukin-18; D053547:Keratin-14; D018664:Interleukin-12; D007371:Interferon-gamma
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