Research Project
10303811
Project Summary/Abstract Allergic asthma is a chronic inflammatory disease of the lungs without cures and effective preventions. Allergen-specific IgE antibodies drive inflammation, airway constriction, and respiratory distress in patients with allergic asthma. Evidence for the existence of a local cellular source of pathogenic IgE in the airway is mounting. However, the precise identity of these cells as well as mechanisms for their localization within the asthmatic lung remain elusive. Using a mouse model of airway hypersensitivity, we have identified a lung- localized population of memory B cell that persists beyond the resolution of inflammation, but rapidly expands upon allergen re-challenge. We hypothesize that these cells are bona fide lung-resident memory B cells that elicit rapid local IgE responses and maintain long-term airway hypersensitivity. In this study, we will 1) elucidate the mechanisms that recruit MBCs and maintain their long-term tissue residency in asthmatic lungs using complementary immune phenotyping, single-cell transcriptomic and imaging analyses; and 2) investigate how functionally lung-resident MBCs contribute to allergic asthma using in vivo depletion of circulating memory B cells and adoptive transfer studies. This study on understanding the biology and functions of tissue-resident memory B cells in asthmatic lungs is imperative, and may reveal new targets for treating and preventing the progression of allergic asthma and other inflammatory lung conditions.
