Author:
Wang Ji,Zhao Yilin,Zhang Xin,Tu Wei,Wan Rongjun,Shen Yingchun,Zhang Yan,Trivedi Ruchik,Gao Peisong
Abstract
RationaleAryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, has been considered as an important regulator for immune diseases. We have previously shown that AhR protects against allergic airway inflammation. The underlying mechanism, however, remains undetermined.ObjectivesWe sought to determine whether AhR specifically in type II alveolar epithelial cells (AT2) modulates allergic airway inflammation and its underlying mechanisms.MethodsThe role of AhR in AT2 cells in airway inflammation was investigated in a mouse model of asthma with AhR conditional knockout mice in AT2 cells (Sftpc-Cre;AhRf/f). The effect of AhR on allergen-induced autophagy was examined by both in vivo and in vitro analyses. The involvement of autophagy in airway inflammation was analyzed by using autophagy inhibitor chloroquine. The AhR-regulated gene profiling in AT2 cells was also investigated by RNA sequencing (RNA-seq) analysis.ResultsSftpc-Cre;AhRf/f mice showed exacerbation of allergen-induced airway hyperresponsiveness and airway inflammation with elevated Th2 cytokines in bronchoalveolar lavage fluid (BALF). Notably, an increased allergen-induced autophagy was observed in the lung tissues of Sftpc-Cre;AhRf/f mice when compared with wild-type mice. Further analyses suggested a functional axis of AhR-TGF-β1 that is critical in driving allergic airway inflammation through regulating allergen-induced cellular autophagy. Furthermore, inhibition of autophagy with autophagy inhibitor chloroquine significantly suppressed cockroach allergen–induced airway inflammation, Th2 cytokines in BALFs, and expression of autophagy-related genes LC3 and Atg5 in the lung tissues. In addition, RNA-seq analysis suggests that autophagy is one of the major pathways and that CALCOCO2/NDP52 and S1009 are major autophagy-associated genes in AT2 cells that may contribute to the AhR-mediated cockroach allergen–induced airway inflammation and, subsequently, allergic asthma.ConclusionThese results suggest that AhR in AT2 cells functions as a protective mechanism against allergic airway inflammation through controlling cell autophagy.
Subject
Immunology,Immunology and Allergy
Reference76 articles.
1. Trends in asthma prevalence, health care use, and mortality in the united states, 2001-2010;Akinbami;NCHS Data Brief,2012
2. Environmental exposures and asthma development: Autophagy, mitophagy, and cellular senescence;Sachdeva;Front Immunol,2019
3. Cockroach allergen exposure and risk of asthma;Do;Allergy,2016
4. Allergen content in German cockroach extracts and sensitization profiles to a new expanded set of cockroach allergens determine in vitro extract potency for IgE reactivity;Glesner;J Allergy Clin Immunol,2019
5. Cockroach allergen component analysis of children with or without asthma and rhinitis in an inner-city birth cohort;Pomes;J Allergy Clin Immunol,2019
Cited by
6 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献