Grant: Project Grant

Asthma is a chronic inflammatory disease affecting >300 million people worldwide and allergic asthma is the most common form. Although most asthmatics are reasonably well controlled by current therapies targeting the inflammatory response, more sophisticated therapies with the ability to reduce the development of asthma and disease exacerbations could impact millions. However, this requires a better understanding of the processes driving these destructive inflammatory responses. We have developed murine models to better understand what happens to the lung after exposure to allergens or respiratory viruses, focusing on two types of models: i) very young mice infected with respiratory syncytial virus, which in humans is associated with development of wheezing and asthma that can persist into adulthood; and ii) adult mice treated with an inflammatory mediator called IL-33, which in humans is implicated in asthma susceptibility and exacerbations. Our data provide evidence that following these exposures, the adult lung is durably changed, such that inflammation develops to normally harmless stimuli. Responses are greater in females, in line with the observation that, in humans, more adult females than males have asthma. We have recently developed methods to purify and phenotype human ILC2s, with which we will evaluate the potential to translate our preclinical observations into novel preventative and therapeutic clinical strategies targeting these cells. We have designed a broad program of research using sophisticated murine models and ex vivo culture of human ILC2s, with the long-term goal of identifying novel targets to reduce asthma susceptibility and disease exacerbations in a sex-specific manner. We are hopeful our research will provide information to guide development of approaches to prevent or reduce increased asthma risk into adulthood associated with early-life respiratory virus exposure and will lead to improved health outcomes for both males and females.