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


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.

Type Journal
ISBN 2589-0042 (Electronic) 2589-0042 (Linking)
Authors Tuong, Z. K.; Lukowski, S. W.; Nguyen, Q. H.; Chandra, J.; Zhou, C.; Gillinder, K.; Bashaw, A. A.; Ferdinand, J. R.; Stewart, B. J.; Teoh, S. M.; Hanson, S. J.; Devitt, K.; Clatworthy, M. R.; Powell, J. E.; Frazer, I. H.
Responsible Garvan Author Prof Joseph Powell
Publisher Name iScience
Published Date 2021-10-31
Published Volume 24
Published Issue 11
Published Pages 103326
Status Published in-print
DOI 10.1016/j.isci.2021.103326
URL link to publisher's version