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.
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