Abstract
Abstract Mobilization of type 2 immune responses is critical to both physiologic tissue remodeling and allergic pathology such as allergic asthma. However, whether there are physical tissue niches with unique cellular constituents that mediate type 2 immunity is unknown. We used quantitative 3D-imaging to define tissue niches of group 2 innate lymphoid cells (ILC2), critical instigators of type 2 immunity. We identified a dominant adventitial ‘cuff’ niche around vessels, airways, and ducts, present in the lung and multiple other tissues. ILC2s, as well as subsets of other tissue-resident hematopoietic cells, localized to these sites. However, ILC2s were most intimately associated with fibroblast-like adventitial stromal cells (ASCs) that were functionally distinct and sufficient to support ILC2 survival and activation. Here we discuss data supporting a model where ILC2s engage in a conversation with micro-anatomically and functionally distinct adventitial mesenchymal cells and other niche components, creating dynamic type 2-biased tissue foci that regulate tissue allergic immunity.
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