John Libbey Eurotext

European Journal of Dermatology


Immunological and structural remodeling in human papillomavirus-induced warts and Bowen disease Article à paraître

Departments of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan,, Departments of Dermatology, Shiga University, Medical Science, Otsu, 520-2192, Japan
  • Mots-clés : human papillomavirus, Bowen disease, dendritic cell, toll-like receptor
  • DOI : 10.1684/ejd.2013.1971

Human papillomavirus-associated warts (HPV-warts) are persistent, evading host immune surveillance. However, these warts sometimes disappear spontaneously, following inflammation. Non-inflamed HPV-warts demonstrated decreased numbers of epidermal Langerhans cells (LCs), low expression levels of MIP3α and E-cadherin, and no apoptotic cells. In the inflamed HPV-warts, on the other hand, various dendritic cell (DC) subsets and many CD8+ cytotoxic T lymphocytes (CTLs) were recruited in association with epidermal MIP3α expression. Many apoptotic keratinocytes were observed in the dermo-epidermal junction. Cellular events were different in HPV-induced Bowen disease (HPV-Bowen): a few LCs were retained in the lesional epidermis, and considerable numbers of B-cells and plasma cells were also observed in the infiltrates, with little or no infiltration of plasmacytoid DCs or dermal/mature DCs. Multiple HPV16-Bowen diseases in the same individuals showed the presence of different sizes of E6/E7-containing cellular transcripts, which indicated that HPV genomes were integrated into the different sites of chromosomes. Toll-like receptor (TLR) 3 was expressed by the lesional keratinocytes even in the non-inflamed HPV-warts, and type 1 interferons (IFNs) were produced in cultured keratinocytes by TLR3 stimulation. HPV-warts are protected from host immune responses and apoptotic signals because they are surrounded by LC-depleted epidermal walls, and viral anti-apoptotic molecules. The up-regulation of epidermal TLR3 signaling might inhibit further HPV spreading.