# Specialized Pro-Resolving Mediator Regulation of NK Cells in Human RSV Bronchiolitis

> **NIH NIH K08** · BRIGHAM AND WOMEN'S HOSPITAL · 2022 · $172,680

## Abstract

Project Summary
Respiratory syncytial virus (RSV) is the major cause of bronchiolitis in pediatric patients and the leading cause
for hospitalization of infants. A subset of RSV-infected children develops overwhelming inflammation that leads
to respiratory failure and even death but the immunobiology underlying this severe phenotype of RSV disease
is incompletely understood. We have found that natural killer (NK) cells are abundant in the airways of RSV-
infected children who have profound inflammation and hypoxemia relative to those with less severe disease.
NK cells are pivotal innate mediators of viral host defense and have important functions in both promoting and
resolving inflammation. NK cells secrete cytokines to recruit leukocytes to sites of active infection but are also
critical effectors of inflammation resolution to later clear activated leukocytes from inflamed tissues to restore
homeostasis. Thus, a balance in the pro-inflammatory and pro-resolving features of NK cells is essential to
both ensure host defense as well as the appropriate resolution of inflammation. Resolution of inflammation is
an active process orchestrated by specialized pro-resolving mediators (SPMs), mediators derived from
essential fatty acids that restrain acute inflammatory responses and signal for resolution, in part by influencing
NK cell function. In work in progress for this proposal, we have found that human NK cells express four distinct
receptors for SPMs and that the SPM lipoxin A4 enhances NK cell resolution functions. We propose a
translational research project to study airway and circulating NK cells in children with severe RSV bronchiolitis
to understand why the natural “braking” signals (i.e. SPMs) are ineffective at controlling virus-induced
inflammation. Our central hypothesis is that the resolution functions of airway NK cells are defective in severe
RSV infection contributing to unrestrained inflammation and are targets for reprogramming by SPMs to
promote resolution. To test this hypothesis, we propose two specific aims: 1) to identify the NK cell molecular
signature associated with severe RSV disease and 2) to determine the impact of SPMs on NK cell resolution
function. We will utilize human pediatric samples from children with RSV-associated respiratory failure to
address these aims. With the guidance and mentorship of Dr. Bruce Levy, Dr. Duvall has developed a four-
year career development plan to provide the mentored research, technical skill development, and tailored
didactic training needed to achieve her goal of becoming an independent physician-scientist. Importantly, this
project will be overseen by a scientific advisory committee with expertise in the study of pulmonary
inflammation, transcriptomic analysis of immune cells, and the effects of SPMs on inflammation resolution,
three key areas of this proposal. This proposal will therefore provide the scientific training and career
development skills to lay the foundation for Dr. Duval...

## Key facts

- **NIH application ID:** 10460167
- **Project number:** 5K08HL145098-04
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Melody G. Duvall
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $172,680
- **Award type:** 5
- **Project period:** 2019-08-01 → 2023-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10460167

## Citation

> US National Institutes of Health, RePORTER application 10460167, Specialized Pro-Resolving Mediator Regulation of NK Cells in Human RSV Bronchiolitis (5K08HL145098-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10460167. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*