PI16 reticular cells in human palatine tonsils govern T cell activity in distinct subepithelial niches.
Journal Paper/Review - May 18, 2023
De Martin Angelina, Stanossek Yves, Lütge Mechthild, Cadosch Nadine, Onder Lucas, Cheng Hung-Wei, Brandstadter Joshua D, Maillard Ivan, Stöckli Sandro, Pikor Natalia, Ludewig Burkhard
Fibroblastic reticular cells (FRCs) direct the interaction and activation of immune cells in discrete microenvironments of lymphoid organs. Despite their important role in steering innate and adaptive immunity, the age- and inflammation-associated changes in the molecular identity and functional properties of human FRCs have remained largely unknown. Here, we show that human tonsillar FRCs undergo dynamic reprogramming during life and respond vigorously to inflammatory perturbation in comparison to other stromal cell types. The peptidase inhibitor 16 (PI16)-expressing reticular cell (PI16 RC) subset of adult tonsils exhibited the strongest inflammation-associated structural remodeling. Interactome analysis combined with ex vivo and in vitro validation revealed that T cell activity within subepithelial niches is controlled by distinct molecular pathways during PI16 RC-lymphocyte interaction. In sum, the topological and molecular definition of the human tonsillar stromal cell landscape reveals PI16 RCs as a specialized FRC niche at the core of mucosal immune responses in the oropharynx.