Tuft Cell Effector Functions in the Intestine

Project Summary/Abstract This grant renewal further investigates the pivotal role of intestinal tuft cells in orchestrating type 2 immune responses. Having previously identified novel tuft cell effector functions that contribute to innate type 2 immunity in the small intestine, the project now delves into the mechanisms by which tuft cells support adaptive immunity. The research encompasses a multi-pronged approach, including elucidating the contributions of tuft cell-secreted mediators like IL-25 and LTC4 to the activation of T helper 2 (Th2) cells. The investigation further extends to exploring tuft cell involvement in various scenarios of adaptive immunity, encompassing cecum and colon regions and memory Th2 cell activation. Additionally, this research endeavors to unveil the potential of tuft cells to induce intestinal pathology, particularly in the context of food allergies. The knowledge gained from this comprehensive analysis is expected to provide crucial insights into the adaptive immune responses mediated by tuft cells, ultimately enabling the development of innovative therapeutic interventions for helminth infections, allergies, and other conditions associated with type 2 immunity in the intestine. The project leverages a custom toolbox and the expertise gained over several years, uniquely positioning the research team to address these critical questions. The proposed study's outcomes promise to enhance our understanding of tuft cell functions and their implications in chronic immune responses, potentially expanding the treatment options for various intestinal pathologies.