# Myeloid cells are critical in inflammatory heart disease

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $599,243

## Abstract

Project Summary/Abstract
Inflammation in the heart causes irreversible cardiac tissue damage. Unlike other organs, a damaged heart
cannot regenerate and can lead to serious health problems. The adult heart contains distinct macrophage
subsets with different functions. We sought to identify a heart macrophage subset highly specialized in tissue
protection. We fully landscaped the immune profile of human pericardial fluid cells using unbiased single cell
level analysis techniques, mass cytometry (CyTOF) and single cell RNA sequencing (scRNA-seq). Given the
well-characterized phenotype and cutting-edge bioinformatic analysis, we predict that Gata6-expressing
macrophages in the pericardial fluid play a heart protective role through tissue repair, efferocytosis, phagocytosis
and immune regulation. The goal of this study is to focus on Gata6+ pericardial macrophages for in-depth studies
of their role in inflammatory and ischemic heart diseases and to identify their cardioprotective mechanisms. In
Aim 1, we will comprehensively characterize the immune phenotype and function of the pericardial effusion cells
including Gata6+ macrophages in patients with or without heart diseases. In our preliminary study, we found a
decrease of Gata6+ macrophages and an increase of memory T cells in the pericardial fluid of ischemic heart
disease and pericarditis patients. We plan to collect 80 pericardial fluid samples from ischemic heart disease,
perimyocarditis and pericarditis patients. We will immune profile the human pericardial fluid cells using CyTOF
and scRNA-seq. We will also determine if the reduction of Gata6+ pericardial macrophages reflects a more
severe disease in these patients by analyzing clinical outcomes. Aim 2 will utilize state-of-the-art macrophage
fate-mapping techniques in the Coxsackievirus B3 (CVB3)-induced myocarditis mouse model to determine the
origin and fate of GATA6+ pericardial macrophages in naïve and viral conditions. The replenishment of GATA6+
pericardial macrophages by blood circulating monocytes will be tested too. Aim 3 will address the mechanism
how Gata6+ pericardial macrophages protect the heart from inflammatory damages using in vivo and in vitro
experimental models. Our preliminary study showed that a selective depletion of Gata6+ pericardial
macrophages worsened myocarditis in mice. We will profile the transcriptomes expressed by cardiac immune
cells and non-hematopoietic stromal cells in Gata6+ macrophage-depleted mice with myocarditis. To prove the
protective role of Gata6+ macrophages, we will test their efferocytosis and anti-inflammatory activity using in vitro
assays. In addition, we will determine the crosstalk between Gata6+ macrophages and cardiac fibroblasts
inhibiting pro-inflammatory monocyte infiltration. This study will reveal (1) a previously unidentified heart
protective macrophage subset in the pericardial cavity, (2) the mechanisms of their tissue protective function,
and (3) the potential of Gata6+ pericar...

## Key facts

- **NIH application ID:** 10057920
- **Project number:** 2R01HL118183-06A1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Daniela Cihakova
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $599,243
- **Award type:** 2
- **Project period:** 2014-02-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10057920

## Citation

> US National Institutes of Health, RePORTER application 10057920, Myeloid cells are critical in inflammatory heart disease (2R01HL118183-06A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10057920. Licensed CC0.

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