Glucocorticoids and development of the immune system

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Stress has major effects on the immune system in all vertebrate animals. In particular, early-life stress can “program” the immune system and have enduring consequences that last into adulthood. Glucocorticoids are steroid hormones that increase in response to environmental stressors. These hormones are secreted by the adrenal glands and, via the blood, reach their targets (for example, the thymus and bone marrow, where important immune cells develop). In addition, recent research shows that glucocorticoids are locally produced within the immune organs themselves, particularly early in life. This surprising discovery raises many interesting and important questions. This research project focuses on the local synthesis of glucocorticoids in immune organs during early development. In particular, how are local glucocorticoid levels regulated by environmental stressors, immune challenges, internal physiological factors, and the microbiome? How do these local glucocorticoids act on immune cells? Do local glucocorticoids have enduring or transient effects? To answer these major questions about the basic biology of this system, this project will integrate multiple cutting-edge techniques, including molecular biology, microbiome bioinformatics, mass spectrometry imaging, and liquid chromatography tandem mass spectrometry. The answers to these important questions will help us understand how stress affects the immune systems of young and adult animals. In addition, the advances in high-throughput mass spectrometry will accelerate endocrine research worldwide and equip future Canadian scientists with key technical skills. The fundamental knowledge gained from this project will have broad impacts on a variety of disciplines, including endocrinology, physiology, neuroscience, microbiology, immunology, and analytical chemistry.