The protective role of GATA6+ pericardial macrophages in pericardial inflammation

David M Hughes; Taejoon Won; Monica V Talor; Hannah M Kalinoski; Ivana Jurčová; Ondrej Szárszoi; Ilja Stříž; Lenka Čurnová; William Bracamonte-Baran; Vojtěch Melenovský; Daniela Čiháková

doi:10.1016/j.isci.2024.110244

The protective role of GATA6⁺ pericardial macrophages in pericardial inflammation

iScience. 2024 Jun 13;27(7):110244. doi: 10.1016/j.isci.2024.110244. eCollection 2024 Jul 19.

Authors

Affiliations

¹ Department of Chemical and Biomolecular Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD 21218, USA.
² Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
³ W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA.
⁴ Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic.

Abstract

Prior research has suggested that GATA6⁺ pericardial macrophages may traffic to the myocardium to prevent interstitial fibrosis after myocardial infarction (MI), while subsequent literature claims that they do not. We demonstrate that GATA6⁺ pericardial macrophages are critical for preventing IL-33 induced pericarditis and attenuate trafficking of inflammatory monocytes and granulocytes to the pericardial cavity after MI. However, absence of GATA6⁺ macrophages did not affect myocardial inflammation due to MI or coxsackievirus-B3 induced myocarditis, or late-stage cardiac fibrosis and cardiac function post MI. GATA6⁺ macrophages are significantly less transcriptionally active following stimulation in vitro compared to bone marrow-derived macrophages and do not induce upregulation of inflammatory markers in fibroblasts. This suggests that GATA6⁺ pericardial macrophages attenuate inflammation through their interactions with surrounding cells. We therefore conclude that GATA6⁺ pericardial macrophages are critical in modulating pericardial inflammation, but do not play a significant role in controlling myocardial inflammation or fibrosis.

Keywords: Biochemistry; Biological sciences; Natural sciences; Physiology; cell biology.