# Function of NLRP3 in regulatory T cell-mediated control of intestinal homeostasis

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $41,567

## Abstract

Project Summary
The inflammasomes are cytoplasmic multi-protein complexes that can sense and be activated by microbes or
tissue damage, which then leads to the activation of caspase-mediated inflammatory pathways involving the
release of cytokines IL-1β and IL-18. Although the pro-inflammatory role of inflammasomes have been well
established in innate immune cells, recently, several studies have uncovered a role for different inflammasome
components in regulating many different T cell responses, a key part of adaptive immunity. Specifically, a
subset of T cells called regulatory T cells (Tregs), which are known for their ability to suppress immune
responses and inflammation, were shown to be affected by their cell intrinsic inflammasome components. Even
though the critical role of Tregs in establishing tolerance to a wide range of innocuous foreign antigens from
commensal microbes and food in the gut has long been well-recognized, the function of the NLRP3
inflammasome in Treg-mediated control of intestinal homeostasis remains an open question. Based on
preliminary data, it was hypothesized that NLRP3/inflammasome could serve as an integral determinant in
controlling Treg biology and that induction of NLRP3 in intestinal Tregs would be specifically required for their
control of Th17 responses in the intestine. To test this hypothesis, the first aim will elucidate the function of
NLRP3 in controlling Treg biology in the gut in heath and disease using both loss-of-function and gain-of-
function approaches through employing two novel mouse models that have been recently generated in the lab:
mice with Treg-specific deletion of NLPR3 and mice with Treg-specific expression of constitutively active
NLRP3. Two different Th17-dependent disease models: anti-CD3 induced intestinal inflammation and
Citrobacter rodentium infection model will be employed. As such, the biological impact of NLRP3 depletion or
constitutive activation in Tregs on the other immune cells in the intestinal system under both physiological and
pathological conditions will be elucidated. In the second aim, the molecular mechanisms underlying NLRP3-
mediated control of Treg biology will be investigated. First, as IL-1b, a component of the NLRP3/inflammasome
pathway was also found to be selectively induced in intestinal Tregs under inflammation, I will determine the
potential role of Treg-derived IL-1b in controlling intestinal homeostasis. Next, the potential involvement of
inflammasome-independent vs. –dependent mechanism underlying NLRP3-mediated Treg biology will also be
examined. Finally, as the heterogeneous nature of Tregs is now well appreciated, Cellular Indexing of
Transcriptomes and Epitopes by Sequencing (CITE-seq) studies will be conducted to determine if there is a
specific subset of Tregs that expresses NLRP3 or whether NLRP3 induction is a common feature for all
intestinal Tregs under inflammation. Collectively, this study will provide mechanistic insights into the
undera...

## Key facts

- **NIH application ID:** 10884222
- **Project number:** 5F31DK135162-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** RASIKA PATKAR
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $41,567
- **Award type:** 5
- **Project period:** 2023-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10884222

## Citation

> US National Institutes of Health, RePORTER application 10884222, Function of NLRP3 in regulatory T cell-mediated control of intestinal homeostasis (5F31DK135162-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10884222. Licensed CC0.

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