# Pro-resolving lipid mediators in immunity and vascular biology

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $524,637

## Abstract

Project Summary/Abstract
 Impaired wound healing is a prominent clinical manifestation of chronic inflammatory diseases, such as
obesity and type 2 diabetes (T2D). Acute wounds in individuals with T2D can become chronic and this is
associated with sustained accumulation of pro-inflammatory leukocytes, prolonged edema, and fibrosis,
leading to impaired wound closure (i.e. re-epithelialization). Functional lymphatic vessels are required for
clearance of immune cells, edema, and host-defense, and several lines of evidence indicate that lymphatic
clearance mechanisms are impaired in obesity and T2D. However, there are no current strategies to resolve
inflammation, improve lymphatic function, and rescue defective tissue repair in obesity and T2D. In health, the
acute inflammatory response that occurs during tissue injury is actively resolved, setting the stage for tissue
repair. Pro-resolving lipid mediators, such as the resolvins, are critical mediators of active resolution of
inflammation in part because they blunt inflammatory cytokine production and stimulate macrophage-mediated
clearance of dead cells. We recently found that resolvins are generated in skin wounds and hasten tissue
repair. Moreover, in work in progress, we discovered that specific receptors for resolvins are expressed on
both macrophages and lymphatic vessels in skin wounds and that resolvin D2 (RvD2) reduces wound edema.
Based on these exciting findings, we hypothesize that RvD2 engages its receptor on macrophages and
lymphatic endothelial cells (LEC) to orchestrate clearance mechanisms during resolution to facilitate tissue
repair. To this end, we propose to elucidate the role of RvD2 and its receptor in resolution of inflammation and
edema during wound healing and determine the relative contribution of macrophages and LEC to this process
by selectively deleting the RvD2 receptor in each cell type in vivo. We will uncover the mechanisms whereby
RvD2 and its receptor regulate functions of macrophages and LEC important for resolution and edema
clearance, and whether these processes can be rescued by RvD2 in obese-diabetic mice. Successful
completion of these studies will uncover completely new roles of RvD2 and its receptor in macrophage and
lymphatic function and could inform novel agonist-based approaches to rescue defective tissue repair in
obesity and T2D, as well as other chronic inflammatory diseases.

## Key facts

- **NIH application ID:** 10052516
- **Project number:** 2R01HL106173-11
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Matthew R Spite
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $524,637
- **Award type:** 2
- **Project period:** 2011-08-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10052516

## Citation

> US National Institutes of Health, RePORTER application 10052516, Pro-resolving lipid mediators in immunity and vascular biology (2R01HL106173-11). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10052516. Licensed CC0.

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