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Persistent transcriptional changes in cardiac adaptive immune cells following myocardial infarction: New evidence from the re-analysis of publicly available single cell and nuclei RNA-sequencing data sets
Journal article   Open access   Peer reviewed

Persistent transcriptional changes in cardiac adaptive immune cells following myocardial infarction: New evidence from the re-analysis of publicly available single cell and nuclei RNA-sequencing data sets

Natasha de Winter, Jiahui Ji, Amalia Sintou, Elvira Forte, Michael Lee, Michela Noseda, Aoxue Li, Andrew L. Koenig, Kory J. Lavine, Sikander Hayat, …
Journal of molecular and cellular cardiology, Vol.192, pp.48-64
07/01/2024
DOI: 10.1016/j.yjmcc.2024.04.016
PMID: 38734060
url
https://doi.org/10.1016/j.yjmcc.2024.04.016View
Published (Version of record) Open Access

Abstract

Chronic immunopathology contributes to the development of heart failure after a myocardial infarction. Both T and B cells of the adaptive immune system are present in the myocardium and have been suggested to be involved in post-MI immunopathology. We analyzed the B and T cell populations isolated from previously published single cell RNA-sequencing data sets (PMID: 32130914, PMID: 35948637, PMID: 32971526 and PMID: 35926050), of the mouse and human heart, using differential expression analysis, functional enrichment analysis, gene regulatory inferences, and integration with autoimmune and cardiovascular GWAS. Already at baseline, mature effector B and T cells are present in the human and mouse heart, having increased activity in transcription factors maintaining tolerance (e.g. DEAF1, JDP2, SPI-B). Following MI, T cells upregulate pro-inflammatory transcript levels (e.g. Cd11, Gzmk, Prf1), while B cells upregulate activation markers (e.g. Il6, Il1rn, Ccl6) and collagen (e.g. Col5a2, Col4a1, Col1a2). Importantly, pro-inflammatory and fibrotic transcription factors (e.g. NFKB1, CREM, REL) remain active in T cells, while B cells maintain elevated activity in transcription factors related to immunoglobulin production (e.g. ERG, REL) in both mouse and human post-MI hearts. Notably, genes differentially expressed in post-MI T and B cells are associated with cardiovascular and autoimmune disease. These findings highlight the varied and time-dependent dynamic roles of post-MI T and B cells. They appear ready-to-go and are activated immediately after MI, thus participate in the acute wound healing response. However, they subsequently remain in a state of pro-inflammatory activation contributing to persistent immunopathology. [Display omitted] •The healthy heart harbours a diverse population of B and T cells, including effector subsets subsets, kept in check by homeostatic transcription factors.•T and B cells are activated immediately after MI and contribute to acute wound healing.•Myocardial T and B cell populations maintain changes in their regulome post-MI, resulting in persistent pro-inflammatory activation.
 Autoimmunity B cells Heart failure Myocardial infarction T cells Transcriptomics

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