Grant: CIHR Fellowship

Lung and respiratory diseases make up 3 of the top 10 causes of death worldwide, and are common across low- and high-income countries. In many cases, such as severe infection or allergy, lethality results from an excessive immune response, while in other cases, lethality results from a reduced immune response and secondary infection. Appropriate regulation of immune activation in the lung is therefore critical in treating infectious and allergic lung disease. Among the most powerful immune regulators are glucocorticoids, stress hormones produced by the adrenal glands. Interestingly, recent work has shown that different tissues, such as the intestine and lung, are also able to produce their own glucocorticoids. Such local production could allow tissue-specific regulation of immunity while avoiding the negative side effects that result from elevated glucocorticoids throughout the body. My research aims to 1) Identify how inflammatory signals cause glucocorticoid production in the lung. 2) Test the mechanisms of lung glucocorticoid production. 3) Test if lung glucocorticoids control the immune response to influenza virus infection. 4) Test if lung glucocorticoids increase the risk of bacterial pneumonia during influenza infection. 5) Test if lung glucocorticoids can be induced to treat allergic asthma. Using mouse strains with genetically altered lung glucocorticoid production, I will examine the effects of infection and allergy on lung tissue and lung-infiltrating immune cells with laboratory techniques including cell culture, gene expression assays, histology, and flow cytometry. These studies will aid our understanding of how immunity is normally regulated in the lung, and will investigate pathways to stimulate lung glucocorticoid production. Stimulation of lung glucocorticoid production could be an effective mechanism for treatment of respiratory infections, allergy, and chronic inflammatory lung diseases such as chronic obstructive pulmonary disease.