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 AhR-mediated 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-β1-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.