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

Chien Hui Hong, Chih Hung Lee, Hsin Su Yu, Shau Ku Huang

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)111-117
Number of pages7
JournalInternational Immunopharmacology
Volume36
DOIs
Publication statusPublished - Jul 1 2016
Externally publishedYes

Fingerprint

Benzopyrenes
Aryl Hydrocarbon Receptors
Langerhans Cells
Hydrocarbons
Smoke
Atopic Dermatitis
Proteins
Cell Movement
Tobacco Products
Ovum
Aryl Hydrocarbon Receptor Nuclear Translocator
T-Lymphocytes
Skin
Inborn Genetic Diseases
Interleukin-13
Interleukin-17
Polycyclic Aromatic Hydrocarbons
Interleukin-5
Environmental Exposure
Xenobiotics

Keywords

  • Aryl hydrocarbon receptor
  • Benzopyrene
  • Epicutaneous protein sensitization
  • Langerhans cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

Cite this

@article{ac41dafb327348cfafd3b59c5238d494,
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.",
keywords = "Aryl hydrocarbon receptor, Benzopyrene, Epicutaneous protein sensitization, Langerhans cells",
author = "Hong, {Chien Hui} and Lee, {Chih Hung} and Yu, {Hsin Su} and Huang, {Shau Ku}",
year = "2016",
month = "7",
day = "1",
doi = "10.1016/j.intimp.2016.04.017",
language = "English",
volume = "36",
pages = "111--117",
journal = "International Immunopharmacology",
issn = "1567-5769",
publisher = "Elsevier",

}

TY - JOUR

T1 - 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

AU - Hong, Chien Hui

AU - Lee, Chih Hung

AU - Yu, Hsin Su

AU - Huang, Shau Ku

PY - 2016/7/1

Y1 - 2016/7/1

N2 - 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.

AB - 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.

KW - Aryl hydrocarbon receptor

KW - Benzopyrene

KW - Epicutaneous protein sensitization

KW - Langerhans cells

UR - http://www.scopus.com/inward/record.url?scp=84964253032&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84964253032&partnerID=8YFLogxK

U2 - 10.1016/j.intimp.2016.04.017

DO - 10.1016/j.intimp.2016.04.017

M3 - Article

VL - 36

SP - 111

EP - 117

JO - International Immunopharmacology

JF - International Immunopharmacology

SN - 1567-5769

ER -