title: 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.
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.
authors.affiliation: Department of Dermatology, National Yang Ming University, Taipei, Taiwan; Department of Dermatology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Chien-Hui
authors.initials: CH
authors.lastname: Hong
authors.affiliation: Department of Dermatology, Kaohsiung, Chang Gung Memorial Hospital, Kaohsiung, Taiwan; Department of Dermatology, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Department of Dermatology, Kaohsiung Medical University, Kaohsiung, Taiwan; National Health Research Institute, Miao-Li, Taiwan.
authors.forename: Hsin-Su
authors.initials: HS
authors.lastname: Yu
authors.affiliation: National Health Research Institute, Miao-Li, Taiwan. Electronic address: skhuang@nhri.org.tw.
authors.forename: Shau-Ku
authors.initials: SK
authors.lastname: Huang
mesh_terms: D000328:Adult; D000485:Allergens / Q000276:immunology; D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000378:metabolism*; D001580:Benzopyrenes / Q000633:toxicity; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D003876:Dermatitis, Atopic / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007114:Immunization; D007801:Langerhans Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D012907:Smoking / Q000009:adverse effects; D058408:Th1-Th2 Balance; D058504:Th17 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000485:Allergens; D001580:Benzopyrenes; D018336:Receptors, Aryl Hydrocarbon; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D010047:Ovalbumin
keywords: Aryl hydrocarbon receptor; Benzopyrene; Epicutaneous protein sensitization; Langerhans cells