# Tuft cell regulation of Peyers patch composition and organization

> **NIH NIH R21** · STANFORD UNIVERSITY · 2023 · $237,763

## Abstract

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.

## Key facts

- **NIH application ID:** 10640203
- **Project number:** 5R21AI171222-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Michael R Howitt
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $237,763
- **Award type:** 5
- **Project period:** 2022-06-08 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10640203

## Citation

> US National Institutes of Health, RePORTER application 10640203, Tuft cell regulation of Peyers patch composition and organization (5R21AI171222-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10640203. Licensed CC0.

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