Benzopyrene, a major polyaromatic hydrocarbon in smoke fume, mobilizes Langerhans cells and polarizes Th2/17 responses in epicutaneous protein sensitization through the aryl hydrocarbon receptor

Int Immunopharmacol. 2016 Jul;36:111-117. doi: 10.1016/j.intimp.2016.04.017. Epub 2016 Apr 27.

Abstract

Background: Atopic dermatitis (AD) is a common disease with genetic and environmental interactions. We previously reported lifetime exposure to cigarette smoke is associated with adult-onset AD. Aryl hydrocarbon receptor (AhR) is important in regulating environmental exposure to xenobiotics, including benzopyrenes (BP), a major polycyclic aromatic hydrocarbon (PAH) present in cigarette smoke. However, how AhR regulates immune responses in sensitization phase of AD remained elusive.

Methods: We investigated how BP affects epicutaneous sensitization response through AhR axis. We compared AhR expression in skin from AD patients and healthy controls. We measured immune responses (Langerhans cell migration and T cell polarization in epicutaneous Ova sensitization in mice with or without AhR defect.

Results: We found AhR and ARNT (AhR nuclear translocator) are upregulated in AD skin. BP exposure increases Langerhans cell migration, and increases IL-5, IL-13, and IL-17 levels when lymph node cells were re-challenged with Ova. The increased cytokine levels were attenuated in AhR defected mice. AhR agonists (BP and ITE) decreased E-cadherin expression, while AhR antagonist (CH223191) increased it in human primary keratinocytes.

Conclusions: These results suggested AhR interacts with BP to polarize T cell responses, along with Langerhans cell migration. This study revealed a regulatory mechanism how cigarette smoking affects atopic sensitization through the benzopyrene-AhR interaction.

Keywords: Aryl hydrocarbon receptor; Benzopyrene; Epicutaneous protein sensitization; Langerhans cells.

MeSH terms

  • Adult
  • Allergens / immunology
  • Animals
  • Aryl Hydrocarbon Receptor Nuclear Translocator / metabolism*
  • Benzopyrenes / toxicity
  • Cell Differentiation
  • Cell Movement
  • Cells, Cultured
  • Dermatitis, Atopic / immunology*
  • Disease Models, Animal
  • Female
  • Humans
  • Immunization
  • Langerhans Cells / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Ovalbumin / immunology
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / metabolism*
  • Skin / metabolism*
  • Skin / pathology
  • Smoking / adverse effects
  • Th1-Th2 Balance
  • Th17 Cells / immunology*
  • Th2 Cells / immunology*

Substances

  • Allergens
  • Benzopyrenes
  • Receptors, Aryl Hydrocarbon
  • Aryl Hydrocarbon Receptor Nuclear Translocator
  • Ovalbumin