# Understanding NLRP6 function in intestinal homeostasis

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $400,174

## Abstract

PROJECT SUMMARY
Nod-like receptors (NLRs) are intracellular pattern-recognition receptors that are involved in host
defense, but have emerged as critical players in the maintenance of tissue homeostasis,
especially within the intestine. Capable of sensing microbial products as well as endogenous
ligands related to tissue injury, NLRs activate multiple downstream inflammatory signaling
pathways, including the inflammasome, to promote the production of cytokines and chemokines
important for pathogen clearance and the timely repair of intestinal epithelial damage. There is
also increasing evidence that NLRs participate in the regulation of the gut microbiome.
Consequently, mice that are deficient in certain NLRs have altered microbiomes associated with
increased susceptibility to colitis and colon tumorigenesis. In particular, mice deficient in NLRP6
develop more severe inflammation and tumors compared to wildtype mice in mouse models of
inflammatory bowel disease and inflammation-associated colon cancer. This phenotype is
associated with impaired IL-18 production and an altered microbiome. However, the cellular
mechanisms by which NLRP6 mediate its protective effects within the colon is unclear. NLRP6
is highly expressed in the epithelium and consistently, there have been multiple reports that
demonstrate epithelial-specific roles for NLRP6, including the production of IL-18, antimicrobial
peptides, and mucus. However, NLRP6 expression can also be induced in hematopoietic cells,
and our published data suggests important roles for NLRP6 in the regulation of IL-18 and intestinal
inflammatory responses in hematopoietic cells. Thus, the mechanism by which NLRP6 protects
against colitis is likely to be complex. The goal of the current proposal is to further delineate
NLRP6 function in myeloid cells and the inflammatory signaling pathways NLRP6 engages in to
affect resistance to intestinal pathology.

## Key facts

- **NIH application ID:** 10141227
- **Project number:** 5R01DK122812-03
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** GRACE Y. CHEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $400,174
- **Award type:** 5
- **Project period:** 2019-07-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10141227

## Citation

> US National Institutes of Health, RePORTER application 10141227, Understanding NLRP6 function in intestinal homeostasis (5R01DK122812-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10141227. Licensed CC0.

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