The mechanisms of ozone-induced eosinophilic airway inflammation in asthma are unclear. The recently discovered group 2 innate lymphocytes (ILC2) are a prominent source of IL-5 and may contribute to airway eosinophilia.
Airway inflammation was assessed from Balb/c mice exposed to Aspergillus fumigatus and/or ozone (2ppm, 2h) and pulmonary ILC2 were isolated by FACS sorting. A549 cells and human sinonasal air liquid interface (ALI) cultures derived from excised nasal polyp tissue were exposed to ozone in vitro (0.9ppm, 1.5h). Freshly harvested atopic and non-atopic nasal tissue was obtained from the Otorhinolaryngology-Head and Neck Surgery Clinic, University of Pennsylvania.
Compared to air exposed controls, ozone significantly amplified airway and lung tissue eosinophilia, increased IL-33, TSLP and IL-5 levels in allergen treated mice (p<0.05, n=6) and induced marked IL-5 mRNA activation in isolated pulmonary ILC2 (p<0.001, n=8). Ozone stimulated IL-33 and TSLP mRNA 1.5 and 6 h later, respectively, in A549 cells but not cells from ALI cultures, suggesting differential sensitivity. Nonetheless, in freshly harvested atopic nasal tissue IL-33 and TSLP mRNA activation was approximately twice as high as in non-atopic nasal tissue, suggesting that nasal epithelial cells are capable of producing these cytokines and this ability might be enhanced in atopic patients.
Ozone induced mRNA for IL-33 and TSLP (activators of ILC2), both in mice and human airway epithelial cells and heightened the expression of IL-5 in murine lung ILC2. We speculate that epithelial activation of ILC2 may be important in mediating the ozone effects on airway eosinophilia.
- AAAAI 2014 (70th)