Aryl hydrocarbon receptor deficiency enhanced airway inflammation and remodeling in a murine chronic asthma model

Yu Di Chang, Ching Hao Li, Chi Hao Tsai, Yu Wen Cheng, Jaw Jou Kang, Chen Chen Lee

Research output: Contribution to journalArticle

Abstract

The aryl hydrocarbon receptor (AhR) is a ligand-dependent-activated transcriptional factor that regulates the metabolism of xenobiotic and endogenous compounds. Recent studies have shown that AhR is a novel master regulator of the mucosal immune system, including lungs and intestine. To elucidate the role of AhR in chronic severe asthma, AhR wild-type and knockout mice (AhR−/−) were sensitized and challenged with ovalbumin for 4 weeks. To uncover the underlying mechanisms, inflammatory cells profile and cytokines production were analyzed in bronchial lavage fluid (BALF) and lung tissue. Compared to wild-type mice, AhR−/− mice had exacerbated asthma symptoms, including airway inflammation, mucus production, airway hyperresponsiveness, and airway remodeling. BALF monocytes, neutrophils, eosinophils, and lymphocytes were all enhanced in OVA-immunized AhR−/− mice. In OVA-immunized AhR−/− mice, T helper (Th) 17 cell-specific cytokine IL-17A, as well as airway remodeling factors, including epithelial-mesenchymal transition (EMT) markers and vascular endothelial growth factor (VEGF), were all enhanced in lung tissue. Moreover, human cohort studies showed that AhR gene expression in bronchial epithelial cells decreases in severe asthma patients. Loss of AhR leads to worsening of allergic asthma symptoms, indicating its importance in maintaining normal lung function and mediating disease severity.

Original languageEnglish
JournalFASEB Journal
DOIs
Publication statusAccepted/In press - 2020

Keywords

  • airway remodeling
  • allergy
  • aryl hydrocarbon receptor
  • epithelial-mesenchymal transition

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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