| First Author | Gosmann C | Year | 2014 |
| Journal | J Invest Dermatol | Volume | 134 |
| Issue | 10 | Pages | 2562-2569 |
| PubMed ID | 24756108 | Mgi Jnum | J:214254 |
| Mgi Id | MGI:5588626 | Doi | 10.1038/jid.2014.201 |
| Citation | Gosmann C, et al. (2014) IL-18, but Not IL-12, Induces Production of IFN-gamma in the Immunosuppressive Environment of HPV16 E7 Transgenic Hyperplastic Skin. J Invest Dermatol 134(10):2562-9 |
| abstractText | 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. |
