# Endothelial Instruction of Macrophage Fate in Inflammatory Injury

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2021 · $127,920

## Abstract

PROJECT SUMMARY/ABSTRACT
There is an emerging recognition that the vasculature is not only a conduit for blood flow but actively modulates
tissue inflammation and repair by interacting with parenchymal and immune cells. The endothelium serves as the
entry point of circulating monocytes transmigrating into the tissue, therefore, endothelial cells (ECs) may modify the
downstream the fate of transmigrated monocytes as they differentiate into distinct tissue macrophage phenotypes.
Considering the importance of macrophages in the propagation and resolution of inflammation, as well as their roles
in tissue repair and regeneration, understanding the interaction between endothelial cells and macrophages may be
of great consequence. We will address mechanisms of generation of how vascular endothelial cells instruct
macrophages and their role in resolving tissue inflammation. We will specifically focus on fundamental questions
such as: What are the EC signals mediating transition to a reparative macrophage phenotype? What signals in
macrophages in turn promote the resolution of inflammation and tissue repair? What are the epigenetic and
transcriptomic features of these phenotype-shifted macrophages? We will test the hypothesis that the endothelium
via Wnt signaling mediates macrophage phenotype transition through modifying mitochondrial metabolism and
epigenome that initiates specific transcriptional programs. In Aim 1, we will define the role of endothelial Wnt
signaling in licensing the differentiation of monocytes to pro-resolving macrophages in inflammatory injury. Here we
will determine the role of the Wnt signaling regulator Rspondin 3 (Rspo3) derived from ECs in signaling the transition
of monocytes to reparative macrophages. In Aim 2, we will determine the role of metabolic reprogramming and
epigenetic modifications of macrophages in mediating phenotype transition and thereby promoting resolution of
inflammatory injury.

## Key facts

- **NIH application ID:** 10144806
- **Project number:** 1R01HL154538-01A1
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Jalees Rehman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $127,920
- **Award type:** 1
- **Project period:** 2021-02-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10144806

## Citation

> US National Institutes of Health, RePORTER application 10144806, Endothelial Instruction of Macrophage Fate in Inflammatory Injury (1R01HL154538-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10144806. Licensed CC0.

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