# Omega-3 fatty acids induce macrophage IL-22 signaling to promote resolution of dust-induced lung inflammation

> **NIH NIH R01** · COLORADO STATE UNIVERSITY · 2023 · $67,235

## Abstract

Project Summary
Inhalation of aerosolized dusts from urban, rural, and farming environments can trigger harmful
airway inflammation and injury; over time, continual exposure to these particulates increases
one’s risk for developing inflammatory airway diseases. While dust exposures negatively impact
lung health, factors contributing to protection versus susceptibility to lung disease following
these continual inhalational exposures are unclear. A recently discovered class of specialized
pro-resolving lipid mediators (SPM) derived from omega-3 fatty acids regulate lung
inflammation, immunity, and repair, and are likely key to the beneficial effects of diets high in
omega-3 fatty acids. Our previous investigations identified that the omega-3 fatty acid
docosahexaenoic acid (DHA) and its lipid metabolite maresin-1 (MaR1) mitigate airway
inflammation from acute and repetitive organic dust exposure, mediated in part by macrophage
activation and pro-repair activities on the airway epithelium. Our exciting new data identify that
omega-3 fatty acids and MaR1 can activate IL-22 signaling in lung macrophages. IL-22
signaling promotes mucosal immunity and epithelial barrier integrity, and its activation in the
presence of these bioactive lipids may be key to their protective effects. Furthermore, our novel
finding of IL-22 signaling in macrophages challenges current dogma regarding the activation
and regulation of this pathway. The goal of this proposal is to investigate the role of omega-3
fatty acids in promoting pro-repair IL-22 signaling in the lung following dust exposures. We
hypothesize that omega-3 fatty acids and SPM promote lung recovery following particulate
matter exposures by inducing alveolar macrophage IL-22 production that subsequently
promotes alveolar macrophage pro-resolution polarization and lung epithelial repair. To test this
hypothesis, in Aim 1, we will establish the impact of omega-3 fatty acids and IL-22 on lung
recovery following dust exposure. In Aim 2, we will evaluate the role of omega-3 fatty acids and
IL-22 in epithelial repair and mucosal immunity during dust exposure. In Aim 3, we will identify
how SPM and IL-22 signaling impacts lung macrophage polarization. Together, our studies will
identify how omega-3 fatty acids modulate susceptibility versus resilience to dust exposures,
including a novel protective mechanism via activation of macrophage IL-22 signaling to promote
tissue repair and mucosal immunity. We expect our studies’ findings to guide novel treatment
strategies for lung disease.

## Key facts

- **NIH application ID:** 10834639
- **Project number:** 3R01HL158926-04S1
- **Recipient organization:** COLORADO STATE UNIVERSITY
- **Principal Investigator:** Tara M Nordgren
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $67,235
- **Award type:** 3
- **Project period:** 2021-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10834639

## Citation

> US National Institutes of Health, RePORTER application 10834639, Omega-3 fatty acids induce macrophage IL-22 signaling to promote resolution of dust-induced lung inflammation (3R01HL158926-04S1). Retrieved via AI Analytics 2026-07-27 from https://api.ai-analytics.org/grant/nih/10834639. Licensed CC0.

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