Innate immunity in the respiratory tract is exquisitely complex and tightly regulated, surveying 10,000 liters of air a day. While canonical pattern-recognition receptors such as toll-like receptors and C-type lectin receptors sense danger in the respiratory mucosa, additional receptor families recognize microbial quorum-sensing molecules, damage-associated molecular patterns, and endogenous lipid mediators. The Barrett Lab is broadly focused on defining the innate immune pathways that contribute to the initiation and persistence of chronic inflammatory disease in the respiratory tract. Our interests include type 2 inflammatory diseases such as allergic asthma or nasal polyposis. Using molecular approaches, murine models, and single cell RNA-Seq analysis of human samples, we study myeloid and epithelial cell signaling, where innate immune receptors are highly expressed.
A longstanding interest of the lab has been to understand the role of cysteinyl leukotrienes (CysLTs), pro-inflammatory lipid mediators, as initiators and amplifiers of innate sensing. These mediators are generated in activated dendritic cells, macrophages, and mast cells, among other cell types. Ongoing work is to define the innate receptors and signaling pathways that elicit CysLT biosynthesis in response to common environmental exposures.
A more recent focus is the airway epithelium. Our studies have revealed a highly significant role for airway epithelial cells in orchestrating sinopulmonary inflammation, and a remarkable degree of airway epithelial remodeling that occurs in respiratory disease. This remodeling leads to both altered epithelial cell environmental sensing and altered functional capacity. In this area, we are trying to define the genetic and epigenetic pathways that govern airway epithelial remodeling, and the functional sequelae of this process.
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