- Dahlgren, Madelene W;
- Jones, Stephen W;
- Cautivo, Kelly M;
- Dubinin, Alexandra;
- Ortiz-Carpena, Jorge F;
- Farhat, Sepideh;
- Yu, Kevin S;
- Lee, Katharine;
- Wang, Chaoqun;
- Molofsky, Anna V;
- Tward, Aaron D;
- Krummel, Matthew F;
- Peng, Tien;
- Molofsky, Ari B
Type 2 lymphocytes promote both physiologic tissue remodeling and allergic pathology, yet their physical tissue niches are poorly described. Here, we used quantitative imaging to define the tissue niches of group 2 innate lymphoid cells (ILC2s), which are critical instigators of type 2 immunity. We identified a dominant adventitial niche around lung bronchi and larger vessels in multiple tissues, where ILC2s localized with subsets of dendritic and regulatory T cells. However, ILC2s were most intimately associated with adventitial stromal cells (ASCs), a mesenchymal fibroblast-like subset that expresses interleukin-33 (IL-33) and thymic stromal lymphopoietin (TSLP). In vitro, ASCs produced TSLP that supported ILC2 accumulation and activation. ILC2s and IL-13 drove reciprocal ASC expansion and IL-33 expression. During helminth infection, ASC depletion impaired lung ILC2 and Th2 cell accumulation and function, which are in part dependent on ASC-derived IL-33. These data indicate that adventitial niches are conserved sites where ASCs regulate type 2 lymphocyte expansion and function.