Langerhans cell homeostasis and activation is altered in hyperplastic human papillomavirus type 16 E7 expressing epidermis

Nor Malia Abd Warif, Patrizia Stoitzner, Graham R. Leggatt, Stephen R. Mattarollo, Ian H. Frazer, Merilyn H. Hibma

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

It has previously been shown that expression of human papillomavirus type 16 (HPV) E7 in epidermis causes hyperplasia and chronic inflammation, characteristics of pre-malignant lesions. Importantly, E7-expressing epidermis is strongly immune suppressed and is not rejected when transplanted onto immune competent mice. Professional antigen presenting cells are considered essential for initiation of the adaptive immune response that results in graft rejection. Langerhans cells (LC) are the only antigen presenting cells located in normal epidermis and altered phenotype and function of these cells may contribute to the immune suppressive microenvironment. Here, we show that LC are atypically activated as a direct result of E7 expression in the epidermis, and independent of the presence of lymphocytes. The number of LC was significantly increased and the LC are functionally impaired, both in migration and in antigen uptake. However when the LC were extracted from K14E7 skin and matured in vitro they were functionally competent to present and cross-present antigen, and to activate T cells. The ability of the LC to present and cross-present antigen following maturation supports retention of full functional capacity when removed from the hyperplastic skin microenvironment. As such, opportunities are afforded for the development of therapies to restore normal LC function in hyperplastic skin.

Original languageEnglish
Article numbere0127155
JournalPLoS One
Volume10
Issue number5
DOIs
Publication statusPublished - 18 May 2015
Externally publishedYes

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Langerhans cells
Human papillomavirus 16
Langerhans Cells
Papillomaviridae
epidermis (animal)
Epidermis
homeostasis
Skin
Homeostasis
Chemical activation
Antigens
skin (animal)
T-cells
Lymphocytes
antigen-presenting cells
Grafts
Antigen-Presenting Cells
antigens
graft rejection
Graft Rejection

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Langerhans cell homeostasis and activation is altered in hyperplastic human papillomavirus type 16 E7 expressing epidermis. / Abd Warif, Nor Malia; Stoitzner, Patrizia; Leggatt, Graham R.; Mattarollo, Stephen R.; Frazer, Ian H.; Hibma, Merilyn H.

In: PLoS One, Vol. 10, No. 5, e0127155, 18.05.2015.

Research output: Contribution to journalArticle

Abd Warif, Nor Malia ; Stoitzner, Patrizia ; Leggatt, Graham R. ; Mattarollo, Stephen R. ; Frazer, Ian H. ; Hibma, Merilyn H. / Langerhans cell homeostasis and activation is altered in hyperplastic human papillomavirus type 16 E7 expressing epidermis. In: PLoS One. 2015 ; Vol. 10, No. 5.
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