Hughes David M, Won Taejoon, Talor Monica V, Kalinoski Hannah M, Jurčová Ivana, Szárszoi Ondrej, Stříž Ilja, Čurnová Lenka, Bracamonte-Baran William, Melenovský Vojtěch, Čiháková Daniela
Department of Chemical and Biomolecular Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD 21218, USA.
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
iScience. 2024 Jun 13;27(7):110244. doi: 10.1016/j.isci.2024.110244. eCollection 2024 Jul 19.
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 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.
先前的研究表明，GATA6心包巨噬细胞可能迁移至心肌，以预防心肌梗死（MI）后的间质纤维化，而后续文献则称它们不会。我们证明，GATA6心包巨噬细胞对于预防IL-33诱导的心包炎至关重要，并可减少MI后炎症单核细胞和粒细胞向心包腔的迁移。然而，缺乏GATA6巨噬细胞并不影响MI或柯萨奇病毒B3诱导的心肌炎所致的心肌炎症，也不影响MI后的晚期心脏纤维化和心脏功能。与骨髓来源的巨噬细胞相比，GATA6巨噬细胞在受到刺激后转录活性显著降低，并且不会诱导成纤维细胞中炎症标志物的上调。这表明GATA6心包巨噬细胞通过与周围细胞的相互作用减轻炎症。因此，我们得出结论，GATA6心包巨噬细胞在调节心包炎症方面至关重要，但在控制心肌炎症或纤维化方面不起重要作用。
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