IL-18, but not IL-12, induces production of IFN-gamma in the immunosuppressive environment of HPV16 E7 transgenic hyperplastic skin

Gosmann, Christina, Frazer, Ian H., Mattarollo, Stephen R. and Blumenthal, Antje (2014) IL-18, but not IL-12, induces production of IFN-gamma in the immunosuppressive environment of HPV16 E7 transgenic hyperplastic skin. Journal of Investigative Dermatology, 134 10: 2562-2569. doi:10.1038/jid.2014.201

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Author Gosmann, Christina
Frazer, Ian H.
Mattarollo, Stephen R.
Blumenthal, Antje
Title IL-18, but not IL-12, induces production of IFN-gamma in the immunosuppressive environment of HPV16 E7 transgenic hyperplastic skin
Formatted title
IL-18, but not IL-12, induces production of IFN-γ in the immunosuppressive environment of HPV16 E7 transgenic hyperplastic skin
Journal name Journal of Investigative Dermatology   Check publisher's open access policy
ISSN 0022-202X
1523-1747
Publication date 2014-05-29
Year available 2014
Sub-type Article (original research)
DOI 10.1038/jid.2014.201
Open Access Status Not yet assessed
Volume 134
Issue 10
Start page 2562
End page 2569
Total pages 8
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Subject 2708 Dermatology
1303 Biochemistry
1307 Cell Biology
1312 Molecular Biology
2700 Medicine
Abstract IFN-gamma has a central role in the defense against infections and cancer. More recently, however, IFN-gamma 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-gamma during infection, the mechanisms that induce IFN-gamma in an immunosuppressive context are unknown. Previously, we identified a key role for IFN-gamma 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-gamma, IL-18, and IL-12 by K14E7 transgenic skin compared with nontransgenic skin. IFN-gamma 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-gamma in K14E7 skin required IL-18 but not IL-12. Our findings show that IL-18 contributes to inducing IFN-gamma in an immunosuppressive cutaneous environment caused by viral oncogene-driven hyperplasia.
Formatted 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.
Keyword Dermatology
Dermatology
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 5U01CA141583
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
UQ Diamantina Institute Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 13 times in Thomson Reuters Web of Science Article | Citations
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Created: Sat, 17 May 2014, 00:53:54 EST by Kylie Hengst on behalf of UQ Diamantina Institute