Document Type
Article
Publication Date
7-1-2024
Original Citation
de Winter N,
Ji J,
Sintou A,
Forte E,
Lee M,
Noseda M,
Li A,
Koenig A,
Lavine K,
Hayat S,
Rosenthal N,
Emanueli C,
Srivastava P,
Sattler S.
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. J Mol Cell Cardiol. 2024;192:48-64.
Keywords
JMG, Myocardial Infarction, Humans, Animals, Single-Cell Analysis, Mice, Myocardium, Sequence Analysis, RNA, B-Lymphocytes, T-Lymphocytes, Adaptive Immunity, Gene Expression Regulation, Gene Expression Profiling, Transcriptome, Transcription, Genetic, Genome-Wide Association Study
JAX Source
J Mol Cell Cardiol. 2024;192:48-64.
ISSN
1095-8584
PMID
38734060
DOI
https://doi.org/10.1016/j.yjmcc.2024.04.016
Abstract
INTRODUCTION: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSION: 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.
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