Langerhans Cells Facilitate UVB-Induced Epidermal Carcinogenesis

J Invest Dermatol. 2015 Nov;135(11):2824-2833. doi: 10.1038/jid.2015.207. Epub 2015 Jun 8.

Abstract

UVB light is considered the major environmental inducer of human keratinocyte (KC) DNA mutations, including within the tumor-suppressor gene p53, and chronic exposure is associated with cutaneous squamous cell carcinoma formation. Langerhans cells (LCs) comprise a dendritic network within the suprabasilar epidermis, yet the role of LCs in UVB-induced carcinogenesis is largely unknown. Herein we show that LC-intact epidermis develops UVB-induced tumors more readily than LC-deficient epidermis. Although levels of epidermal cyclopyrimidine dimers following acute UVB exposure are equivalent in the presence or absence of LCs, chronic UVB-induced p53 mutant clonal islands expand more readily in association with LCs, which remain largely intact and are preferentially found in proximity to the expanding mutant KC populations. The observed LC facilitation of mutant p53 clonal expansion is completely αβ and γδ T-cell independent and is associated with increased intraepidermal expression of IL-22 and the presence of group 3 innate lymphoid cells. These data demonstrate that LCs have a key role in UVB-induced cutaneous carcinogenesis and suggest that LCs locally stimulate KC proliferation and innate immune cells that provoke tumor outgrowth.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biopsy, Needle
  • Carcinogenesis / pathology*
  • Cell Proliferation / radiation effects*
  • Cells, Cultured
  • Disease Models, Animal
  • Epidermis / pathology
  • Epidermis / radiation effects*
  • Female
  • Flow Cytometry
  • Gene Expression Regulation
  • Humans
  • Immunohistochemistry
  • Interleukin-22
  • Interleukins / metabolism
  • Interleukins / radiation effects
  • Langerhans Cells / pathology
  • Langerhans Cells / radiation effects*
  • Mice
  • Mice, Inbred Strains
  • Skin Neoplasms / etiology*
  • Skin Neoplasms / pathology
  • Ultraviolet Rays / adverse effects*

Substances

  • Interleukins