title: Dendritic cell subsets and immunological milieu in inflammatory human papilloma virus-related skin lesions.
abstract: BACKGROUND
  Human papilloma virus (HPV)-related warts persist, evading host immune surveillance, but sometimes disappear with inflammation.
  
  
  OBJECTIVE
  To elucidate the immune evasion mechanisms of HPV, we have examined the density, dynamics, and subsets of dendritic cell (DC) types in non-inflammatory or inflammatory HPV-related skin lesions such as warts and Bowen's disease (HPV-Bowen), and compared the epidermal expression levels of macrophage inflammatory protein (MIP)-3α and E-cadherin.
  
  
  METHODS
  The expression of various DC markers, MIP-3α, and E-cadherin in the tissue samples obtained from patients with warts, HPV-Bowen and HPV-unrelated skin diseases was evaluated by immunohistochemistry. MIP-3α gene expression levels were examined in warts and HPV-Bowen by in situ hybridization (ISH) and real-time quantitative polymerase chain reaction (RT-qPCR).
  
  
  RESULTS
  The numbers of Langerhans cells (LCs) and the expression levels of MIP-3α and E-cadherin were decreased in non-inflammatory warts and HPV-Bowen, as compared with normal skin. Both epidermal LCs and MIP-3α expression reappeared in inflammatory warts, associated with dermal infiltrates composed of many cytotoxic T cells and various subsets of DCs, while cellular infiltrates in HPV-Bowen contained many B cells and plasma cells with sparse infiltration of DCs. The upregulation of MIP-3α gene expression was confirmed in the inflammatory warts and HPV-Bowen by ISH and RT-qPCR.
  
  
  CONCLUSIONS
  The depletion of LCs in the non-inflammatory warts and HPV-Bowen is associated with a down-regulation of expression levels of MIP-3α and E-cadherin in the lesional keratinocytes. MIP-3α expression is upregulated in lesional keratinocytes of inflammatory warts, with the subsequent recruitment of various DC subsets and cytotoxic T cells, whereas plasma cell-rich infiltration was induced in HPV-Bowen.
authors.affiliation: Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Nakayama
authors.forename: Kenji
authors.initials: K
authors.lastname: Asagoe
authors.forename: Akiko
authors.initials: A
authors.lastname: Yamauchi
authors.forename: Takenobu
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Shirafuji
authors.forename: Shin
authors.initials: S
authors.lastname: Morizane
authors.forename: Gen
authors.initials: G
authors.lastname: Nakanishi
authors.forename: Keiji
authors.initials: K
authors.lastname: Iwatsuki
mesh_terms: D017209:Apoptosis; D001483:Base Sequence; D001913:Bowen's Disease / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000821:virology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D054418:Chemokine CCL20 / Q000235:genetics / Q000378:metabolism; D015344:DNA Probes, HPV / Q000235:genetics; D003713:Dendritic Cells / Q000145:classification* / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D015603:Keratinocytes / Q000473:pathology; D017492:Keratosis, Seborrheic / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D030361:Papillomavirus Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D017193:Skin Diseases, Viral / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014860:Warts / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: C108355:CCL20 protein, human; D015820:Cadherins; D054418:Chemokine CCL20; D015344:DNA Probes, HPV