# ILC3 Syndecan-4 in the Regulation of Intestinal Health and Inflammation

> **NIH NIH F31** · WEILL MEDICAL COLL OF CORNELL UNIV · 2024 · $48,974

## Abstract

PROJECT SUMMARY
Inflammatory bowel disease (IBD) arises when gut microbes elicit inappropriate immune responses in the
intestine, leading to chronic inflammation and tissue damage. As cases rise worldwide, it is important to identify
the pathways that restrain these responses and promote mucosal healing. Critically, group 3 innate lymphoid
cells (ILC3s) are a recently identified cell type which is enriched in the healthy intestine and becomes
dysregulated during IBD, colon cancer and other chronic inflammatory disorders. Further, mouse models have
revealed fundamental roles for ILC3s in controlling immune tolerance, immunity, and inflammation in the
intestine. Despite these advances, the mechanisms by which ILC3s sense and respond to the intricate milieu of
signals present in the intestinal mucosa to coordinate intestinal health, impact inflammation, or promote tissue
healing remains unclear and represents an important area of future investigation. In new preliminary data, I have
unexpectedly determined that ILC3s are uniquely enriched in expression of a cell surface heparan sulfate
proteoglycan receptor, syndecan-4, a pathway linked to wound healing, cell migration/adhesion, and control of
growth factor signaling. Further, I identified a cellular and molecular mechanism regulating syndecan-4 on ILC3s
and discovered that syndecan-4 becomes dysregulated in experimental mouse models of intestinal inflammation
or human IBD. Finally, mice lacking ILC3-specific syndecan-4 show greater tissue damage and susceptibility to
intestinal inflammation. This provokes a novel hypothesis that syndecan-4 is a critical pathway impacting ILC3
biology, host-microbiota homeostasis, and tissue repair during intestinal health and inflammation. The
fundamental focus of this research proposal is to test this hypothesis and define the regulation and functional
significance of ILC3-specific syndecan-4 by employing novel mouse models, innovative technical approaches,
and translational studies. It is expected that the results from the two aims of this proposal will reveal crucial
signaling mechanisms for inflammatory responses in the intestine that may have therapeutic potential for the
treatment of IBD.

## Key facts

- **NIH application ID:** 10806978
- **Project number:** 5F31DK134187-02
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Brooke Elizabeth Towers
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 5
- **Project period:** 2023-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10806978

## Citation

> US National Institutes of Health, RePORTER application 10806978, ILC3 Syndecan-4 in the Regulation of Intestinal Health and Inflammation (5F31DK134187-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10806978. Licensed CC0.

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