Dendritic cell subsets and immunological milieu in inflammatory human papilloma virus-related skin lesions

J Dermatol Sci. 2011 Sep;63(3):173-83. doi: 10.1016/j.jdermsci.2011.05.006. Epub 2011 Jun 6.

Abstract

Background: Human papilloma virus (HPV)-related warts persist, evading host immune surveillance, but sometimes disappear with inflammation.

Objectives: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Base Sequence
  • Bowen's Disease / genetics
  • Bowen's Disease / immunology
  • Bowen's Disease / metabolism
  • Bowen's Disease / virology
  • Cadherins / genetics
  • Cadherins / metabolism
  • Chemokine CCL20 / genetics
  • Chemokine CCL20 / metabolism
  • DNA Probes, HPV / genetics
  • Dendritic Cells / classification*
  • Dendritic Cells / immunology*
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Keratinocytes / pathology
  • Keratosis, Seborrheic / genetics
  • Keratosis, Seborrheic / immunology
  • Keratosis, Seborrheic / metabolism
  • Papillomavirus Infections / genetics
  • Papillomavirus Infections / immunology*
  • Papillomavirus Infections / metabolism
  • Real-Time Polymerase Chain Reaction
  • Skin Diseases, Viral / genetics
  • Skin Diseases, Viral / immunology*
  • Skin Diseases, Viral / metabolism
  • Warts / genetics
  • Warts / immunology
  • Warts / metabolism

Substances

  • CCL20 protein, human
  • Cadherins
  • Chemokine CCL20
  • DNA Probes, HPV