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Yu Zhang’s laboratory, Dr. Jiangping Song’s team from Fuwai Hospital and Dr. Mingyao Li from University of Pennsylvania collaborated in dissecting the immunological network of autoimmune myocarditis by Single-cell RNA sequencing

Publication Date:2020/05/27

On May 20, 2020, Dr. Yu Zhang’s laboratory, Dr. Jiangping Song’s team from Fuwai Hospital and Dr. Mingyao Li from University of Pennsylvania collaborated in publishing a paper titled "Single-Cell RNA Sequencing to Dissect the Immunological Network of Autoimmune Myocarditis " in Circulation. A comparison of scRNA-seq data from different EAM phases suggests that some cell clusters, such as macrophage cluster 2 and Th17 cells, are associated with the inflammatory response in the EAM model. The Hif1a expression level correlates with the extent of the inflammatory response. PX-478, a Hif1a inhibitor, alleviates inflammation of different EAM phases and may serve as a potential therapeutic target in the clinic.

Myocarditis can develop into dilated cardiomyopathy (DCM), which may require heart transplantation (HTx). The immunological network of myocarditis phases remains unknown. This study aimed to investigate the immunological network during the transition from myocarditis to cardiomyopathy and to identify the genes contributing to the inflammatory response to myocarditis.

We identified 26 cell subtypes among 34,665 cells. Macrophages constituted the main immune cell population at all disease phases (greater than 60%), and an inflammation associated macrophage cluster was identified in which the expression of Hif1a-regulated genes was upregulated. The neutrophil population was increased after the induction of EAM, and neutrophils then released Il-1 to participate in the EAM process. T cells were observed at the highest percentage at the subacute inflammatory phase. Th17 cells, in which the expression of Hif1a-regulated genes was upregulated, constituted the main T cell population detected at the acute inflammatory phase, while Treg cells were the main T cell population detected at the subacute inflammatory phase, and γδ T cells releasing Il-17 were the main T cell population observed at the myopathy phase (Figure 1).


Figure 1. Single-cell RNA sequencing to dissect the immune cell populations from different stages of EAM model.

The Hif1a expression level correlated with the extent of inflammation. Additionally, PX-478 could alleviate the inflammatory responses of the different EAM phases (Figure 2). Finally, HIF1A was expressed at higher levels in acute autoimmune myocarditis patients than in DCM patients and healthy controls


Figure 2. Hif1a as the hallmark TF in EAM inflammationand PX-478, a Hif1a inhibitor , could alleviate the inflammatory responses of the different EAM phases

We herein present a comprehensive single-cell landscape of the cardiac immune cells in different EAM phases. In addition, we elucidated the contribution of Hif1a to the inflammatory response through the regulation of immune cell activity, particularly of macrophage cluster 2 and Th17 cells. Moreover, a Hif1a inhibitor alleviated inflammatory cell infiltration of the EAM model and may serve as a potential therapeutic target in the clinic.

Xiumeng Hua in Fuwai Hospital, Gang Hu in Nankai University and Qingtao Hu in Dr. Yu Zhang’s lab, are co-first authors of this paper. Dr. Yu Zhang, Dr. Mingyao Li and Dr. Jiangping Song are the corresponding authors. Other contributing authors include Yuan Chang and Dr. Yiqing Hu from Fuwai Hospital and Linlin Gao from Dr. Yu Zhang’s lab.