A model of impaired Langerhans cell maturation associated with HPV induced epithelial hyperplasia

Summary: Langerhans cells (LC) are skin-resident antigen-presenting cells that regulate immune responses to epithelial microorganisms. Human papillomavirus (HPV) infection can promote malignant epithelial transformation. As LCs are considered important for controlling HPV infection, we compared the...

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Autores principales:	Zewen K. Tuong, Samuel W. Lukowski, Quan H. Nguyen, Janin Chandra, Chenhao Zhou, Kevin Gillinder, Abate A. Bashaw, John R. Ferdinand, Benjamin J. Stewart, Siok Min Teoh, Sarah J. Hanson, Katharina Devitt, Menna R. Clatworthy, Joseph E. Powell, Ian H. Frazer
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Biological sciences Immune system Bioinformatics Transcriptomics Science Q
Acceso en línea:	https://doaj.org/article/08f0ec2087624af0b1807e9af63d460a
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spelling	oai:doaj.org-article:08f0ec2087624af0b1807e9af63d460a2021-11-20T05:09:58ZA model of impaired Langerhans cell maturation associated with HPV induced epithelial hyperplasia2589-004210.1016/j.isci.2021.103326https://doaj.org/article/08f0ec2087624af0b1807e9af63d460a2021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221012955https://doaj.org/toc/2589-0042Summary: Langerhans cells (LC) are skin-resident antigen-presenting cells that regulate immune responses to epithelial microorganisms. Human papillomavirus (HPV) infection can promote malignant epithelial transformation. As LCs are considered important for controlling HPV infection, we compared the transcriptome of murine LCs from skin transformed by K14E7 oncoprotein and from healthy skin. We identified transcriptome heterogeneity at the single cell level amongst LCs in normal skin, associated with ontogeny, cell cycle, and maturation. We identified a balanced co-existence of immune-stimulatory and immune-inhibitory LC cell states in normal skin that was significantly disturbed in HPV16 E7-transformed skin. Hyperplastic skin was depleted of immune-stimulatory LCs and enriched for LCs with an immune-inhibitory gene signature, and LC-keratinocyte crosstalk was dysregulated. We identified reduced expression of interleukin (IL)-34, a critical molecule for LC homeostasis. Enrichment of an immune-inhibitory LC gene signature and reduced levels of epithelial IL-34 were also found in human HPV-associated cervical epithelial cancers.Zewen K. TuongSamuel W. LukowskiQuan H. NguyenJanin ChandraChenhao ZhouKevin GillinderAbate A. BashawJohn R. FerdinandBenjamin J. StewartSiok Min TeohSarah J. HansonKatharina DevittMenna R. ClatworthyJoseph E. PowellIan H. FrazerElsevierarticleBiological sciencesImmune systemBioinformaticsTranscriptomicsScienceQENiScience, Vol 24, Iss 11, Pp 103326- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biological sciences Immune system Bioinformatics Transcriptomics Science Q
spellingShingle	Biological sciences Immune system Bioinformatics Transcriptomics Science Q Zewen K. Tuong Samuel W. Lukowski Quan H. Nguyen Janin Chandra Chenhao Zhou Kevin Gillinder Abate A. Bashaw John R. Ferdinand Benjamin J. Stewart Siok Min Teoh Sarah J. Hanson Katharina Devitt Menna R. Clatworthy Joseph E. Powell Ian H. Frazer A model of impaired Langerhans cell maturation associated with HPV induced epithelial hyperplasia
description	Summary: Langerhans cells (LC) are skin-resident antigen-presenting cells that regulate immune responses to epithelial microorganisms. Human papillomavirus (HPV) infection can promote malignant epithelial transformation. As LCs are considered important for controlling HPV infection, we compared the transcriptome of murine LCs from skin transformed by K14E7 oncoprotein and from healthy skin. We identified transcriptome heterogeneity at the single cell level amongst LCs in normal skin, associated with ontogeny, cell cycle, and maturation. We identified a balanced co-existence of immune-stimulatory and immune-inhibitory LC cell states in normal skin that was significantly disturbed in HPV16 E7-transformed skin. Hyperplastic skin was depleted of immune-stimulatory LCs and enriched for LCs with an immune-inhibitory gene signature, and LC-keratinocyte crosstalk was dysregulated. We identified reduced expression of interleukin (IL)-34, a critical molecule for LC homeostasis. Enrichment of an immune-inhibitory LC gene signature and reduced levels of epithelial IL-34 were also found in human HPV-associated cervical epithelial cancers.
format	article
author	Zewen K. Tuong Samuel W. Lukowski Quan H. Nguyen Janin Chandra Chenhao Zhou Kevin Gillinder Abate A. Bashaw John R. Ferdinand Benjamin J. Stewart Siok Min Teoh Sarah J. Hanson Katharina Devitt Menna R. Clatworthy Joseph E. Powell Ian H. Frazer
author_facet	Zewen K. Tuong Samuel W. Lukowski Quan H. Nguyen Janin Chandra Chenhao Zhou Kevin Gillinder Abate A. Bashaw John R. Ferdinand Benjamin J. Stewart Siok Min Teoh Sarah J. Hanson Katharina Devitt Menna R. Clatworthy Joseph E. Powell Ian H. Frazer
author_sort	Zewen K. Tuong
title	A model of impaired Langerhans cell maturation associated with HPV induced epithelial hyperplasia
title_short	A model of impaired Langerhans cell maturation associated with HPV induced epithelial hyperplasia
title_full	A model of impaired Langerhans cell maturation associated with HPV induced epithelial hyperplasia
title_fullStr	A model of impaired Langerhans cell maturation associated with HPV induced epithelial hyperplasia
title_full_unstemmed	A model of impaired Langerhans cell maturation associated with HPV induced epithelial hyperplasia
title_sort	model of impaired langerhans cell maturation associated with hpv induced epithelial hyperplasia
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/08f0ec2087624af0b1807e9af63d460a
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A model of impaired Langerhans cell maturation associated with HPV induced epithelial hyperplasia

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