# Role of IRF1 in NLRP3 inflammasome activation and inflammatory diseases

> **NIH NIH K22** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $162,000

## Abstract

Abstract
 Perturbation of homeostasis, as a result of pathogen invasion or self imbalance, can result in tissue
damage and chronic inflammation. In addition to its well-established role in clearance of pathogens or cell
corpses, inflammation also promotes tissue repair and regeneration. Conserved from flies to humans, a transient
and properly terminated inflammatory response is crucial for restoration of tissue homeostasis after damage and
its absence enhances tissue damage, leading to severe immunopathology. A key player in normal and
pathological inflammation is the NLRP3 inflammasome, a major sensor of tissue damage, toxic substances and
certain pathogens. Aberrant NLRP3 inflammasome activation has been shown to promote the development of
gouty arthritis, lupus, atherosclerosis, Alzheimer's disease, macular degeneration and cancer. It is therefore of
utmost importance to study the molecular mechanism involved in NLRP3 inflammasome activation during health
and disease. NLRP3 inflammasome activation occurs via two distinct steps: “priming” and “activation”. Although
different events involved in the “activation” step have been identified, the signaling steps through which NLRP3
inflammasome is activated remains unclear. Even less is understood about “priming”, which entails synthesis of
the caspase-1 substrate pro-IL-1β as well as elevated NLRP3 expression. Recently, I identified interferon
regulatory factor 1 (IRF1) as a novel player that is required for NLRP3 inflammasome activation. Of note, LPS-
mediated priming results in strong IRF1 induction whereas IRF1 ablation prevents NLRP3 activation without
affecting expression of pro-IL-1β or components of the inflammasome. This proposal aims at delineating the
entire signaling pathway through which IRF1 controls NLRP3 inflammasome activation, and determining the role
of this pathway in the pathogenesis of NLRP3-associated inflammatory disorders. Completion of this study will
not only further our knowledge on inflammasome biology, but also provide a new way to interfere with aberrant
NLRP3 inflammasome activation in a number of inflammatory diseases.

## Key facts

- **NIH application ID:** 9599233
- **Project number:** 1K22AI135074-01A1
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Zhenyu Zhong
- **Activity code:** K22 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $162,000
- **Award type:** 1
- **Project period:** 2020-09-24 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9599233

## Citation

> US National Institutes of Health, RePORTER application 9599233, Role of IRF1 in NLRP3 inflammasome activation and inflammatory diseases (1K22AI135074-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9599233. Licensed CC0.

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