A Model of Impaired Langerhans Cell Maturation Associated With HPV Induced Epithelial Hyperplasia

Langerhans cells (LC) are skin-resident antigen-presenting that regulate immune responses to epithelial commensal and pathogenic microorganisms. Infection of skin by human papillomavirus (HPV) is commonly persistant can promote malignant transformation. As LCs considered important in control HPV infection, we compared the transcriptome from transformed oncogenic E7 protein HPV16 healthy skin. We identified heterogeneity at single cell level amongst normal mouse skin, associated with ontogeny, cycle activity, maturation. a balanced co-existence immune-stimulatory immune-inhibitory LC states was signficantly disturbed E7-expressing hyperproliferative murine Hyperplastic depleted LCs, enriched for an gene signature, LC-keratinocyte cross-talk dysregulated. reduced expression CSF1R ligand interleukin (IL)-34, critical molecule homeostasis. Enrichment signature levels IL-34 were also found HPV-associated cervical cancers. transgenic hyperplastic thus provides robust model investigate interventions overcome impaired maturation induced proliferation cancer.