# NOD-like Receptors in Intestinal Inflammation

> **NIH NIH P01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $352,468

## Abstract

ABSTRACT
The discovery of innate immune receptors has revolutionized the field of innate immunity. An unexpected
finding is that innate immune receptor are not only located on the cell membrane, but a majority of these are
found intracellularly. This allows cells to detect intracellular perturbation from pathogen-associated molecular
patterns (PAMPs) or from damage-associated molecular patterns (DAMPs). Our studies have revealed a
novel roles of intracellular innate immune receptor in attenuating inflammation and shaping the microbiome
during inflammatory bowel disease (IBD). The central hypothesis is that the bi-directional interplay of inhibitory
intracellular innate receptors with the microbiome is a major contributing factor in IBD. Our proposal focuses on
the intracellular NLR (nucleotide-binding domain, leucine-rich repeat containing protein, or NOD-like receptor)
proteins. While NOD2 remains the most prominent in Crohns’ disease, we have focused on the role of other
NLRs in colitis. We have data to show that several inhibitory NLR proteins strongly mitigate intestinal
inflammation by reducing the activation of immune signaling pathway thus preventing an inflammatory cytokine
response that is integral to colitis. This in turn can affect both innate and adaptive immune cells, as well as
colon epithelial cells. We have also shown that these inhibitory NLRs affect the microbiome, partly by
maintaining bacteria that can contain a pro-inflammatory response. Thus the first goal is to understand the
bidirectional interaction of inhibitory NLR and the gut microbiota in mitigating gut inflammation in mice by
working with Projects 2, 4 and the Animal Models Core A. Another over-arching goal is to assess the
translational relevance of results obtained in mice to humans. Working with Project 3 and the Human Tissue
and Genomics Core B, we will analyze patient-derived material to verify the significance of our findings in mice
to inflammatory bowel disease patient samples.

## Key facts

- **NIH application ID:** 10216239
- **Project number:** 5P01DK094779-08
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Jenny P Ting
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $352,468
- **Award type:** 5
- **Project period:** 2013-09-19 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10216239

## Citation

> US National Institutes of Health, RePORTER application 10216239, NOD-like Receptors in Intestinal Inflammation (5P01DK094779-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10216239. Licensed CC0.

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