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Aryl hydrocarbon receptor in airway epithelium exacerbates cockroach allergen-induced asthma through autophagy
Monday, March 6, 2017: 3:00 PM
Rooms B303-B304 (Georgia World Congress Center, Building B)
Yilin Zhao, MD PhD, , , , , , ,
Rationale: Aryl hydrocarbon receptor (AhR), a receptor for common environmental contaminants, is an important regulator of immune responses. Our previous studies have suggested a role of AhR in protecting against cockroach allergen-induced lung inflammation by using AhR-/- mice. Autophagy plays a major role in controlling immune responses and inflammation. We sought to determine whether the activated AhR signaling specifically in airway epithelium by cockroach allergen modulates cockroach allergen-induced lung inflammation through autophagy

Methods: The role of AhR expressed in epithelium in cockroach allergen (CRE) induced allergic inflammation was investigated in a mouse model of asthma with AhR epithelial conditional knock out mice (ftpc-Cre;AhRflox/flox). Cockroach allergen induced the activation of AhR and autophagy signaling in epithelium was determined. The role of autophagy in CRE-induced asthma was also investigated.

Results: CRE-challenged Sftpc-Cre; AhRflox/flox mice displayed decreased lung infiltrates, mucus production, and airway hyper-responsiveness. These mice also showed reduced levels of IL-4, IL-5, IL-13, IL-17, but increased IL-10 and IL-22 in the BAL fluids. Decreased IC3B II in airways was also observed. Moreover, CRE can activate AhR (CYP1A1 and CYP1B1) and autophagy (Beclin-1, Atg5, and p62) signaling in epithelial cells in vitro, and AhR agonist TCDD can potentiate CRE-induced autophagy. Furthermore, CRE-induced lung inflammation was significantly suppressed when autophagy inhibitor was used in the mouse model with decreased lung infiltrates and Th2/T17 cytokines in BAL fluids.

Conclusions: Contrast to the protective role previously observed in AhR-/- mice, AhR in airway epithelial may exacerbate CRE-induced inflammation, which may through activating autophagy signaling.