# Mechanisms of Macrophage Functional Switch during Skin Repair

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA-IRVINE · 2020 · $207,240

## Abstract

Background. Macrophages support skin wound healing by switching their function from pro-
inflammatory to anti-inflammatory and tissue remodeling ones. This mechanism is deranged in
pathological states including chronic ulcers and skin cancer. However, the mechanisms underlying the
functional change of tissue macrophages in health and disease are undefined in vivo due to the lack of
suitable animal models, thus posing a formidable hurdle towards the development of therapies aiming at
reorienting macrophage functions.
Hypothesis. We hypothesize a central role of functional reprogramming of individual macrophages
from pro- to non-inflammatory functions, as opposed to expansion and contraction of macrophage
populations with invariable function, in governing skin wound healing. We also hypothesize that
alteration of macrophage functions, possibly in concert with their impaired migration within the skin,
underlies the pathophysiology of diabetic ulcers and melanoma.
Aims. In Aim 1 we will develop strategies to map the functional fate of pro-inflammatory macrophages
(PRImap mice), and use them to quantify the contribution of macrophage reprogramming to the
generation of reparative and anti-inflammatory macrophages during wound healing. Aim 2 is dedicated
to understand how macrophage function and reprogramming correlates with their motility and location
within the skin, and how these aspects may be uncoupled in diabetic ulcers and melanoma.
Experimental Design. We will quantify pro-inflammatory macrophage reprogramming to restorative or
anti-inflammatory functions by wounding healthy or diabetic mice or injecting melanomas in PRImap
mice, using FACS and histological analysis. The motility of pro-inflammatory and reprogrammed
macrophages in health and disease will be studied through intravital microscopy.
Expected results. We expect to identify which mechanism among macrophage reprogramming, local
proliferation of anti-inflammatory macrophages or recruitment of anti-inflammatory monocytes is the
driving force of the macrophage functional switch that supports skin wound healing. We will further
establish whether pro-inflammatory or reprogrammed macrophages display altered migration in diabetic
ulcers and melanoma, contributing to their pathophysiology.
Impact. Our study will contribute to the areas of basic immunology and immunotherapy by defining the
extent of macrophage reprogramming, and whether it is the main mechanism underlying macrophage
functional and migratory changes in physiologic and pathologic contexts. In the long term, PRImap mice
will be valuable to identify the molecular determinants of macrophage reprogramming, thus paving the
way to the manipulation of macrophage functions for therapeutic purposes.

## Key facts

- **NIH application ID:** 10011758
- **Project number:** 5R21AR072849-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Francesco Marangoni
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $207,240
- **Award type:** 5
- **Project period:** 2019-09-06 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10011758

## Citation

> US National Institutes of Health, RePORTER application 10011758, Mechanisms of Macrophage Functional Switch during Skin Repair (5R21AR072849-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10011758. Licensed CC0.

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