Aryl hydrocarbon receptor protects lungs from cockroach allergen-induced inflammation by modulating mesenchymal stem cells

Ting Xu, Yufeng Zhou, Lipeng Qiu, Danh C. Do, Yilin Zhao, Zhuang Cui, Heng Wang, Xiaopeng Liu, Arjun Saradna, Xu Cao, Mei Wan, Peisong Gao

Research output: Contribution to journalArticle

Abstract

Exposure to cockroach allergen leads to allergic sensitization and increased risk of developing asthma. Aryl hydrocarbon receptor (AhR), a receptor for many common environmental contaminants, can sense not only environmental pollutants but also microbial insults. Mesenchymal stem cells (MSCs) are multipotent progenitor cells with the capacity to modulate immune responses. In this study, we investigated whether AhR can sense cockroach allergens and modulate allergen-induced lung inflammation through MSCs. We found that cockroach allergen-treated AhR-deficient (AhR-/-) mice showed exacerbation of lung inflammation when compared with wild-type (WT) mice. In contrast, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an AhR agonist, significantly suppressed allergen-induced mouse lung inflammation. MSCs were significantly reduced in cockroach allergen-challenged AhR-/- mice as compared with WT mice, but increased in cockroach allergen-challenged WT mice when treated with TCDD. Moreover, MSCs express AhR, and AhR signaling can be activated by cockroach allergen with increased expression of its downstream genes cyp1a1 and cyp1b1. Furthermore, we tracked the migration of i.v.-injected GFP+ MSCs and found that cockroach allergen-challenged AhR-/- mice displayed less migration of MSCs to the lungs compared with WT. The AhRmediated MSC migration was further verified by an in vitro Transwell migration assay. Epithelial conditioned medium prepared from cockroach extract-challenged epithelial cells significantly induced MSC migration, which was further enhanced by TCDD. The administration of MSCs significantly attenuated cockroach allergen-induced inflammation, which was abolished by TGF-b1- neutralizing Ab. These results suggest that AhR plays an important role in protecting lungs from allergen-induced inflammation by modulating MSC recruitment and their immune-suppressive activity.

Original languageEnglish (US)
Pages (from-to)5539-5550
Number of pages12
JournalJournal of Immunology
Volume195
Issue number12
DOIs
StatePublished - Dec 15 2015

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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