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
; 192: 48-64, 2024 Jul.
Article
en En
| MEDLINE
| ID: mdl-38734060
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Linfocitos B
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Análisis de Secuencia de ARN
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Análisis de la Célula Individual
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Infarto del Miocardio
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Miocardio
Límite:
Animals
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Humans
Idioma:
En
Revista:
J Mol Cell Cardiol
/
J. mol. cell. cardiol
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Journal of molecular and cellular cardiology
Año:
2024
Tipo del documento:
Article
País de afiliación:
Reino Unido