# The role of GPR84 signaling during skin repair

> **NIH NIH R01** · GEORGE WASHINGTON UNIVERSITY · 2024 · $455,856

## Abstract

ABSTRACT
 Efficient wound healing requires complex cellular communication between tissue-resident
non-immune cells and infiltrating immune cells. While much has been learned about how
cytokines and growth factors contribute to acute wound healing, we know very little about how
lipid signaling regulates acute inflammation and tissue repair, and identification of new
mechanisms that govern acute inflammation and repair is needed. We previously demonstrated
that inhibiting dermal adipocyte lipolysis led to reduced macrophage numbers during early
inflammation and delayed repair, yet the mechanism(s) linking adipocyte lipolysis to efficient
inflammation and repair have not been identified. Given the rising numbers of diabetic and aged
patients, it is imperative to define molecular underpinnings that promote a healthy acute
inflammatory response and to identify druggable mechanisms to treat inflammation and non-
healing wounds.
 Inhibition of injury-induced dermal adipocyte lipolysis significantly reduces the abundance
of medium-chain fatty acids (MCFAs). Recently, GPR84 was identified to be an MCFA receptor
that is expressed by bone marrow-derived myeloid cells and during tissue inflammation. Activation
of GPR84 in vitro increases macrophage migration and enhances pro-inflammatory gene
expression; however, its role in skin and the in vivo mechanism of action is not well defined. We
observe increased GPR84-expression during wound-induced inflammation and found that
administration of a GPR84 agonist increases macrophage numbers. Additionally, systemic
administration of a GPR84 antagonist decreases wound bed macrophages and delays tissue
repair. Based on our preliminary data, we hypothesize that GPR84 signaling is required to support
macrophage numbers and subsequent repair during injury-induced inflammation. We will
combine our team’s tools and expertise in adipocyte, keratinocyte, and macrophage biology with
single-cell data interrogation to validate this hypothesis with the following Specific Aims: (1) Use
mouse models to determine how GPR84 signaling controls macrophage numbers and
subsequent tissue repair after injury, and (2) define how MCFA/GPR84 signaling directly
regulates myeloid cell function during skin wound healing and (3) define how epithelial GPR84
signaling contributes to keratinocyte function after injury.
 GPR84 signaling represents a new window to better understand mechanisms that regulate
the injury response. Findings from this proposed work could lay a solid foundation for developing
new tools that predict and enhance therapeutic treatment of wound healing.

## Key facts

- **NIH application ID:** 10795018
- **Project number:** 5R01AR082417-02
- **Recipient organization:** GEORGE WASHINGTON UNIVERSITY
- **Principal Investigator:** BRETT SHOOK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $455,856
- **Award type:** 5
- **Project period:** 2023-03-01 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10795018

## Citation

> US National Institutes of Health, RePORTER application 10795018, The role of GPR84 signaling during skin repair (5R01AR082417-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10795018. Licensed CC0.

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