IL-17 suppresses immune effector functions in human papillomavirus-associated epithelial hyperplasia

Gosmann, Christina, Mattarollo, Stephen R., Bridge, Jennifer A., Frazer, Ian H. and Blumenthal, Antje (2014) IL-17 suppresses immune effector functions in human papillomavirus-associated epithelial hyperplasia. Journal of Immunology, 193 5: 2248-2257. doi:10.4049/jimmunol.1400216

Author Gosmann, Christina
Mattarollo, Stephen R.
Bridge, Jennifer A.
Frazer, Ian H.
Blumenthal, Antje
Title IL-17 suppresses immune effector functions in human papillomavirus-associated epithelial hyperplasia
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 1550-6606
Publication date 2014-09-01
Year available 2014
Sub-type Article (original research)
DOI 10.4049/jimmunol.1400216
Open Access Status DOI
Volume 193
Issue 5
Start page 2248
End page 2257
Total pages 10
Place of publication Bethesda, MD, United States
Publisher American Association of Immunologists
Language eng
Abstract Persistent infection with high-risk human papillomaviruses (HPV) causes epithelial hyperplasia that can progress to cancer and is thought to depend on immunosuppressive mechanisms that prevent viral clearance by the host. IL-17 is a cytokine with diverse functions in host defense and in the pathology of autoimmune disorders, chronic inflammatory diseases, and cancer. We analyzed biopsies from patients with HPV-associated cervical intraepithelial neoplasia grade 2/3 and murine skin displaying HPV16 E7 protein-induced epithelial hyperplasia, which closely models hyperplasia in chronic HPV lesions. Expression of IL-17 and IL- 23, a major inducer of IL-17, was elevated in both human HPV-infected and murine E7-expressing lesions. Using a skingrafting model, we demonstrated that IL-17 in HPV16 E7 transgenic skin grafts inhibited effective host immune responses against the graft. IL-17 was produced by CD3+T cells, predominantly CD4+T cells in human, and CD4+and γδ T cells in mouse hyperplastic lesions. IL-23 and IL-1β, but not IL-18, induced IL-17 production in E7 transgenic skin. Together, these findings demonstrate an immunosuppressive role for IL-17 in HPV-associated epithelial hyperplasia and suggest that blocking IL-17 in persistent viral infection may promote antiviral immunity and prevent progression to cancer.
Keyword Immunology
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 080214
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Chemistry and Molecular Biosciences
UQ Diamantina Institute Publications
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