HPV16-E7 expression in squamous epithelium creates a local immune suppressive environment via CCL2- and CCL5- mediated recruitment of mast cells

Bergot, Anne-Sophie, Ford, Neill, Leggatt, Graham R., Wells, James W., Frazer, Ian H. and Grimbaldeston, Michele A. (2014) HPV16-E7 expression in squamous epithelium creates a local immune suppressive environment via CCL2- and CCL5- mediated recruitment of mast cells. PLoS Pathogens, 10 10: 1-11. doi:10.1371/journal.ppat.1004466


Author Bergot, Anne-Sophie
Ford, Neill
Leggatt, Graham R.
Wells, James W.
Frazer, Ian H.
Grimbaldeston, Michele A.
Title HPV16-E7 expression in squamous epithelium creates a local immune suppressive environment via CCL2- and CCL5- mediated recruitment of mast cells
Journal name PLoS Pathogens   Check publisher's open access policy
ISSN 1553-7374
1553-7366
Publication date 2014-10-23
Year available 2014
Sub-type Article (original research)
DOI 10.1371/journal.ppat.1004466
Open Access Status DOI
Volume 10
Issue 10
Start page 1
End page 11
Total pages 11
Place of publication San Francisco, United States
Publisher Public Library of Science
Collection year 2015
Language eng
Abstract Human Papillomavirus (HPV) 16 E7 protein promotes the transformation of HPV infected epithelium to malignancy. Here, we use a murine model in which the E7 protein of HPV16 is expressed as a transgene in epithelium to show that mast cells are recruited to the basal layer of E7-expressing epithelium, and that this recruitment is dependent on the epithelial hyperproliferation induced by E7 by inactivating Rb dependent cell cycle regulation. E7 induced epithelial hyperplasia is associated with increased epidermal secretion of CCL2 and CCL5 chemokines, which attract mast cells to the skin. Mast cells in E7 transgenic skin, in contrast to those in non-transgenic skin, exhibit degranulation. Notably, we found that resident mast cells in E7 transgenic skin cause local immune suppression as evidenced by tolerance of E7 transgenic skin grafts when mast cells are present compared to the rejection of mast cell-deficient E7 grafts in otherwise competent hosts. Thus, our findings suggest that mast cells, recruited towards CCL2 and CCL5 expressed by epithelium induced to proliferate by E7, may contribute to an immunosuppressive environment that enables the persistence of HPV E7 protein induced pre-cancerous lesions.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article # e1004466

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 12 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 11 times in Scopus Article | Citations
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Created: Fri, 24 Oct 2014, 09:55:24 EST by Dr Graham Leggatt on behalf of UQ Diamantina Institute