# Tuft cell heterogeneity in function, lineage, and structure in ileal inflammatory disease

> **NIH NIH R01** · VANDERBILT UNIVERSITY · 2021 · $597,365

## Abstract

PROJECT SUMMARY/ABSTRACT
Inflammatory Bowel Disease (IBD) and its subtype Crohn’s disease (CD) arise due to a loss of
tolerance to environmental antigens in genetically susceptible individuals. Longitudinal analysis
has identified an inverse correlation between rates of communicable parasitic diseases and IBD,
a phenomenon termed the “hygiene hypothesis.” Tuft cells have recently been identified as a
critical component for sensing and responding to parasitic infections. Our lab has recently
identified that tuft cells may be heterogeneous in their lineage and function in microbiome
response, and specific populations may be critical for mitigating inflammation in ileal inflammatory
disease. Here, we propose innovative experimental and computational approaches to dissect the
heterogeneity of tuft cell lineage, structure, and function as they relate to regulating immune
responses in in vivo models of CD. In aim 1, we will conduct single-cell sequencing, high
resolution microscopy, and functional secretory assays to understand lineage-structure-function
relationships in different tuft cell populations in mouse and enteroid models. In aim 2, we utilize
multiplex imaging, Cytometry Time-of-Flight (CyTOF), and cytokine profiling to probe the
downstream tuft-type 2 response network by utilizing several chemical and genetic models of
pathway ablation. Through our findings, we aim to make significant contributions to the current
understanding of tuft cell biology and epithelial-microbiome crosstalk in the intestine. Ultimately,
this research will allow us to diagnose, stratify, and, ultimately, treat patients with IBD and expand
the pool of targets in this complex, multifactorial disease.

## Key facts

- **NIH application ID:** 10048223
- **Project number:** 2R01DK103831-06
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Ken S Lau
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $597,365
- **Award type:** 2
- **Project period:** 2016-02-15 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10048223

## Citation

> US National Institutes of Health, RePORTER application 10048223, Tuft cell heterogeneity in function, lineage, and structure in ileal inflammatory disease (2R01DK103831-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10048223. Licensed CC0.

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