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
0022-1767
Publication date 2014-09-01
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
Collection year 2015
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.
Q-Index Code C1
Q-Index Status Confirmed Code
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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