# Epigenetic regulation of intestinal tuft cells

> **NIH NIH R01** · CINCINNATI CHILDRENS HOSP MED CTR · 2024 · $627,541

## Abstract

Intestinal epithelial cells reside at the direct interface between the microbiota and mammalian
host, and are thus uniquely poised to sense microbial signals that calibrate intestinal immunity
and function. Tuft cells are a specialized epithelial cell that have recently been shown to respond
to microbial stimuli and initiate and amplify type 2 immune responses in the intestine. However,
despite a clear relationship between the microbiota and intestinal health, the mechanisms
underlying how the microbiota instruct tuft cell homeostasis and function remain poorly
understood. Epigenetics represent a central mechanism that can potentially link microbial triggers
in the pathogenesis of intestinal disease. Consistent with this concept, we previously identified
that epithelial loss of an epigenetic-modifying enzyme disrupted microbiota-sensitive intestinal
homeostasis and increased susceptibility to intestinal damage. Our new preliminary data suggest
that regulation of tuft cell development and homeostasis may be epigenetically regulated and
dynamically controlled by distinct metabolites produced by the intestinal microbiota. Based on
these findings, we hypothesize that (1) tuft cell responses in the intestine may be calibrated by
distinct components of the microbiota through an epigenetic sensor and that (2) epigenetic
mechanisms in stem cells may regulate tuft cell development and function. To investigate these
hypotheses, we will (i) interrogate how distinct commensal bacterial-derived metabolites instruct
intestinal stem cell differentiation to tuft cells through an epigenetic-modifying enzyme, and (ii)
directly identify and investigate new mechanisms by which the stem cell epigenetic landscape
can be modulated to control tuft cell differentiation in the intestine. This work will uncover novel
epigenetically-regulated pathways that direct tuft cell biology in the intestine, and therefore guide
personalized approaches for treating intestinal diseases.

## Key facts

- **NIH application ID:** 10994224
- **Project number:** 1R01DK137771-01A1
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Theresa Alenghat
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $627,541
- **Award type:** 1
- **Project period:** 2024-08-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10994224

## Citation

> US National Institutes of Health, RePORTER application 10994224, Epigenetic regulation of intestinal tuft cells (1R01DK137771-01A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10994224. Licensed CC0.

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