Tuft cell regulation of Peyers patch composition and organization

点击翻译按钮获取中文摘要

Project Summary Peyer’s patches are gastrointestinal-associated lymphoid tissues found in the small intestine that function as critical induction sites of antigen-specific immunity in the gut. Food and microbial antigens are actively transported from the intestinal lumen and delivered to underlying immune cells in Peyer’s patches by specialized microfold (M) cells within the follicular-associated epithelium (FAE). To facilitate the acquisition of intestinal antigens, the FAE has a thin mucus layer with dramatically fewer goblet cells compared to the adjoining villous epithelium. Furthermore, the FAE is mostly devoid of other specialized epithelial subsets found in the villi, including Paneth cells and enteroendocrine cells, but whether tuft cells populate the FAE remains unknown. We and others found that villous tuft cells use their unique chemosensory capabilities to detect parasites and initiate type 2 immunity and tissue remodeling. Our preliminary data shows that the FAE contains numerous tuft cells, which can influence the immune cell populations in the Peyer’s patch. Therefore, we hypothesize that tuft cells act as microbial sentinels that shape the cellular composition and organization of Peyer’s patches. In Aim 1, we will employ a novel reporter mouse strain to examine the influence of tuft cells and symbiotic protists on M cell development and heterogeneity. In Aim 2, we identify tuft cell-mediated changes to the immune cell composition and spatial organization in Peyer’s patches. We have assembled a team with expertise in all the major areas of this proposal, including Dr. Eugene Butcher, who is an expert on immune cell trafficking in mucosal and lymphoid tissues. Together these studies will reveal an previously unrecognized role for tuft cells in Peyer’s patch biology and provide a foundation to understand how tuft cells influence antigen-specific immune responses to enteric pathogens and mucosal vaccines.