# Characterization of E. coli-specific T cells in Crohn's disease

> **NIH NIH R21** · BENAROYA RESEARCH INST AT VIRGINIA MASON · 2022 · $259,450

## Abstract

PROJECT SUMMARY/ABSTRACT
Several lines of evidence have implicated T cells in the pathogenesis of Crohn's disease, an uncontrolled
inflammatory condition of the intestines in which immune cells overreact to the bacteria that live there.
Previous studies of antigen-nonspecific T cells in Crohn's disease have not identified overall differences in
them that would explain this over reactivity. However, we have recently identified CD4 T cells of the immune
system that can react to a peptide from protein antigen (OmpC) made by one such bacteria (E. coli), to which
antibodies are commonly seen only in people with Crohn's disease. We found that these OmpC-specific cells
make IL-10 unless they come from Crohn's disease patients, and hypothesize that this defect plays a central
role in the inflammation of Crohn's disease. IL-10 is a cytokine that clearly plays a central role in limiting
inflammation in the intestines, because mice without the IL-10 gene and humans born with a mutation in the
receptor for IL-10 both quickly develop severe enterocolitis, resembling Crohn's disease. The overall goal of
the studies proposed here is to determine why these gut flora antigen-specific T cells fail to make IL-10 in
Crohn's disease, as a mechanism by which tolerance to gut flora is lost in this condition. The novel approach
is to integrate single cell gene expression and epigenetic analyses in these OmpC-specific T cells we can
isolate with MHC-II tetramers. The hypothesis will be addressed in two Specific Aims with genome-wide
expression differences correlated with IL-10 expression in Aim 1, and an epigenetic basis for failed IL-10
expression in Crohn's disease to be revealed in Aim 2. Together these studies will advance our understanding
of abnormal IL-10 regulation by gut microbial antigen-specific T cells in Crohn's disease, and provide the
foundation for determining how such a defect contributes to disease pathogenesis.

## Key facts

- **NIH application ID:** 10452471
- **Project number:** 1R21AI164332-01A1
- **Recipient organization:** BENAROYA RESEARCH INST AT VIRGINIA MASON
- **Principal Investigator:** James Daniel Lord
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $259,450
- **Award type:** 1
- **Project period:** 2022-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10452471

## Citation

> US National Institutes of Health, RePORTER application 10452471, Characterization of E. coli-specific T cells in Crohn's disease (1R21AI164332-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10452471. Licensed CC0.

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