Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
de, Winter, N; Ji, J; Sintou, A; Forte, E; Lee, M; Noseda, M; Li, A; Koenig, AL; 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;
Doi: 10.1016/j.yjmcc.2024.04.016
Web of Science
PubMed
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- Führende Autor*innen der Med Uni Graz
- Sattler Susanne
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- 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 analysed the B and T cell populations isolated from previously published single cell 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. Il-6, 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 the mouse and human post-MI heart. 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.
- Find related publications in this database (Keywords)
- Myocardial infarction
- Heart failure
- B cells
- T cells
- Autoimmunity
- Transcriptomics