# Age-associated Innate Immune Dysfunction in Chronic Rhinosinusitis

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2021 · $611,877

## Abstract

Project Summary
Chronic rhinosinusitis (CRS) is a common inflammatory disease that affects a large portion of the U.S.
population, resulting in poor quality of life for those affected and utilizing billions of dollars of health care
resources. Unfortunately, CRS presents more like a heterogeneous syndrome than a distinct diagnostic entity,
resulting in variability in both phenotype, symptoms, and inflammatory signatures. Consequently, CRS
pathophysiology and associated mechanisms of disease remain poorly understood. Our group recently identified
a unique inflammatory signature specific to elderly CRS patients, which is characterized by profound elevation
of IL-1 and other pro-inflammatory cytokines. The central hypothesis of this proposal is that CRS in aged
patients is associated with an age-dependent, IL-1-associated mechanism that derives from dysfunctional
innate immunity and activation of the inflammasome. We will test this hypothesis by analyzing a large
prospectively enrolled cohort of CRS patients. Specific Aim 1 will determine whether aging is associated with
altered Toll-like receptor expression or function, with resultant ‘priming’ of the innate immune system. Aim 2 will
determine whether aging in CRS patients results in increased inflammasome activation. We will subsequently
analyze the ability of common microbial ligands and endogenous age-related inflammatory stimuli to activate
inflammasome-associated cytokine production and release. Finally, in Specific Aim 3 we will determine whether
there are functional associations between the sinonasal microbiome and/or individual pathogens with aging,
innate immune function, and the IL-1-driven pro-inflammatory signature. This proposal seeks to characterize a
previously unrecognized inflammatory subtype of CRS that affects aged individuals, a vulnerable population with
limited medical and surgical options. Findings from this study will provide further insight into the mechanism of
CRS and reveal previously unidentified associations between innate immune function, the sinus microbiota, and
different types of chronic mucosal inflammation in the sinonasal cavity.

## Key facts

- **NIH application ID:** 10259879
- **Project number:** 5R01AG065550-02
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Justin H Turner
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $611,877
- **Award type:** 5
- **Project period:** 2020-09-10 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10259879

## Citation

> US National Institutes of Health, RePORTER application 10259879, Age-associated Innate Immune Dysfunction in Chronic Rhinosinusitis (5R01AG065550-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10259879. Licensed CC0.

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