Ph.D., Pharmacology, National Taiwan University;
Instructor in Pediatrics, Harvard Medical School;
Research Associate in Immunology, Boston Children's Hospital
Studies of asthma have been limited by a poor understanding of how nonallergic environmental exposures, such as air pollution and infection, are translated in the lung into inflammation and wheezing. Our goal was to understand the mechanism of nonallergic asthma that leads to airway hyperreactivity (AHR), a cardinal feature of asthma independent of adaptive immunity. We examined mouse models of experimental asthma in which AHR was induced by respiratory syncytial virus infection or ozone exposure using mice deficient in T-cell immunoglobulin and mucin domain 1 (TIM1/HAVCR1), an important asthma susceptibility gene. TIM12/2 mice did not have airways disease when infected with RSVor when repeatedly exposed to ozone, a major component of air pollution. On the other hand, the TIM12/2 mice had allergen-induced experimental asthma, as previously shown. The RSV- and ozone-induced pathways were blocked by treatment with caspase inhibitors, indicating an absolute requirement for programmed cell death and apoptosis. TIM-1– expressing, but not TIM-1–deficient, natural killer T cells.