# Modulation of the biliary immune niche by the microbiome

> **NIH NIH K22** · UNIVERSITY OF WISCONSIN-MADISON · 2024 · $108,000

## Abstract

PROJECT SUMMARY/ABSTRACT
Biliary tract disease and inflammation, including pediatric biliary atresia and primary sclerosing cholangitis, are
leading causes of liver failure. Chronic biliary inflammation, which can be associated with the presence of
gallstones, is a risk factor for development of cholangiocarcinoma, a rare but deadly malignancy. Acute
inflammation of the gallbladder, or cholecystitis, accounts for 20% of all biliary tract disease hospitalizations,
usually requires surgical intervention and has significant mortality if left untreated. Together, biliary tract disease,
including common gallstones, represents an enormous human health burden. Biliary tract inflammation plays
clear roles in progression of various common and rare biliary diseases, however our understanding of
inflammation and immune processes within the biliary tract are exceedingly limited.
The resident immune cell populations in the extrahepatic biliary tree at homeostasis have never been
characterized, and whether host or environmental factors can influence the development of the biliary niche has
never been explored. It is unknown if resident biliary immune cells could impact development and progression
of biliary disease. During my postdoctoral training, I developed a reproducible tissue digest method that yields
highly viable immune, epithelial, and stromal cell populations. Single cell RNA sequencing revealed that there is
a diversity of resident immune cells present at homeostasis in the mouse gallbladder/extrahepatic bile ducts,
including innate lymphoid cells, adaptive lymphocytes, neutrophils, macrophages, and dendritic cells. In the
course of studying biliary tuft cells—rare, chemosensory epithelial cells with known immunomodulating
properties—I found that the biliary immune niche is altered in the absence of tuft cells, and is also sensitive to
the microbiome-status of the host. My data suggest that the microbiome and biliary epithelial cells (including tuft
cells) regulate the establishment of the biliary immune niche. In this proposal, I will test the role of the microbiome
and microbial metabolites in setting biliary immune “tone,” and will define a role for tuft cells in regulating the
biliary immune cell make-up. I will test whether alterations in the biliary immune niche at homeostasis, specifically
the presence or absence of neutrophils, can impact the progression of cholesterol gallstone disease. To
accomplish these aims, I have formed collaborations with experts in liver/biliary biology and microbiome
manipulations, and have established a career development plan that will facilitate increasing computational
independence. These studies will reveal new links between host factors and biliary inflammation, with the
potential for therapeutic targeting of biliary epithelial cells and the microbiome to impact biliary health and
disease.

## Key facts

- **NIH application ID:** 10872107
- **Project number:** 5K22AI166029-02
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** CLAIRE E O'LEARY
- **Activity code:** K22 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $108,000
- **Award type:** 5
- **Project period:** 2023-06-20 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10872107

## Citation

> US National Institutes of Health, RePORTER application 10872107, Modulation of the biliary immune niche by the microbiome (5K22AI166029-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10872107. Licensed CC0.

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