Patrick J Brennan
By the time we see patients in the clinic, pathology is usually established, and the flames of inflammation are already burning. What keeps inflammation going, and can we do anything about it? The central theme of our laboratory is to understand the regulation and maintenance of effector T cells in allergic and inflammatory diseases. We are studying 1) the transcriptional regulation of effector T cell function and 2) the regulation of T cell effector function by the local environment. The long-term goal of these studies is to identify key effector pathways that we can target with specific therapeutics.
The first research area we are exploring is the regulation of human Th2 effector T cells. It has recently become clear that allergic disease is driven by subsets of highly differentiated Th2 effector cells. Using single cell transcriptomics from severe, Th2-driven human asthma as a starting point, we have identified novel pathways that regulate pathogenic Th2 effector T cells. We have also identified a new and unexpected effector axis by which airways Th2 T cells instruct the respiratory epithelium. This work involves close collaboration with other faculty in the Division of Allergy and Clinical Immunology at Brigham and Women's Hospital.
The second area of research in the lab is focused on the biology of innate T cells. Up to 20% of T cells in humans are innate-like, conserved between individuals, and recognize conserved microbial or environmental antigens. These innate T cell populations influence a wide range of immune responses from host defense to allergic disease. We are using transcriptomics to define how innate T cells maintain a poised effector state. We are also studying the regulation of invariant natural killer T cells (model innate T cells) by factors in the gut environment. Starting with human intestinal contents from across early childhood, we are using a multi-omics approach driven primarily by untargeted mass spectrometry to identify factors in the human gut that are associated with food allergy. We have identified novel lipid antigens for natural killer T cells in both the diet and microbiota, and we are investigating how lipids and other metabolites in the gut environment affect iNKT cells and adaptive immune tolerance. This line of research includes several fantastic collaborators at Brigham and Women's Hospital, Children's Hospital Boston, and the Harvard School of Public Health.
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