# Cytokine regulation of intestinal epithelial restitution

> **NIH NIH R01** · CHILDREN'S HOSPITAL OF LOS ANGELES · 2020 · $7,304

## Abstract

PROJECT SUMMARY
Inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis, is a chronic
inflammatory disorder of the gastrointestinal tract. IBD afflicts nearly 1.5 million people in the United States.
The exact causes of IBD are unknown, but they are thought to generally involve dysregulated host immune
responses to commensal microorganisms in genetically susceptible individuals. Tumor necrosis factor (TNF), a
major immune cytokine, has a central role in the disease process. While anti-TNF therapies are a part of the
medical regimen for many IBD patients, there is mounting evidence that the complete blockade of TNF
signaling is not appropriate in the long-term for many. For example, most patients treated with anti-TNF
biologics stop responding to the therapy within 5 years. We and others have demonstrated that TNF signaling
through its lesser-characterized receptor TNFR2 has many beneficial functions on the repair of the colonic
epithelial barrier, a crucial mitigating aspect of IBD, and on the regulation of immune cells including cytotoxic
(CD8+) T lymphocytes and regulatory T cells. This application will follow-up on these novel observations to
explore the mechanisms that underlie TNFR2's protective effects on CD8+ T cells and colonic epithelial stem
cell populations in the setting of colonic injury and inflammation. Specifically, we will: 1) determine the
mechanisms by which TNFR2 regulates the pathogenicity of CD8+ T cells in colitis, 2) elucidate the role of
TNFR2 in regulation of CD8+ T cell subpopulations and their colonic localization, and 3) define the role of
epithelial TNFR2 on colonic epithelial stem cell dynamics and mucosal healing. These studies will reveal
important cellular and molecular patterns that may underlie the pathophysiology of IBD.

## Key facts

- **NIH application ID:** 9978770
- **Project number:** 5R01DK056008-22
- **Recipient organization:** CHILDREN'S HOSPITAL OF LOS ANGELES
- **Principal Investigator:** D Brent Polk
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $7,304
- **Award type:** 5
- **Project period:** 1999-08-15 → 2020-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9978770

## Citation

> US National Institutes of Health, RePORTER application 9978770, Cytokine regulation of intestinal epithelial restitution (5R01DK056008-22). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9978770. Licensed CC0.

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