ArticleFrontiers in immunology2022
Crosstalk between cytotoxic CD8+ T cells and stressed cardiomyocytes triggers development of interstitial cardiac fibrosis in hypertensive mouse hearts.
Article in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 24 citations in OpenAlex.
- Endothelial Filamin C Alleviates Atherosclerosis via PINK1/Parkin-Dependent Mitophagy and mtDNA-cGAS-STING Inflammation Suppression.Journal of cardiovascular development and disease · 2026Article
- Macrophage-Dependent Intercellular Crosstalk in Multiphenotypic Heart Failure With Preserved Ejection Fraction.Journal of the American Heart Association · 2026Review
- Emerging roles of the cGAS/STING pathway in cardiovascular diseases.The Journal of clinical investigation · 2026Review
- Beyond Reperfusion: Early Molecular Drivers and Therapeutic Opportunities in Acute Post-Infarction Cardiac Fibrosis.International journal of molecular sciences · 2026Review
- CD8Nature reviews. Cardiology · 2026Review
- Microvascular endothelial scavenger receptor class B type I protects against heart failure with preserved ejection fraction by inhibiting T-cell cardiotropism.EMBO molecular medicine · 2026Article
- Dynamic Organelle Remodeling in HIV-Associated Myocardial Disease: Mechanisms, Fibrotic Pathways, and Therapeutic Opportunities.Current issues in molecular biology · 2026Review
- Association between T cell exhaustion and the recurrence of atrial fibrillation after cryoballoon ablation.Frontiers in immunology · 2026Article
- CCL5 promotes angiotensin II-induced cardiac remodeling through regulation of platelet-driven M2 macrophage polarization.Theranostics · 2026Article
- Immune Cell-Mediated Inflammation in Heart Failure: Subset Heterogeneity and Targeted Therapy.International journal of general medicine · 2026Review
- PHD2 Deletion in CD8Hypertension (Dallas, Tex. : 1979) · 2025Article
- Identification of early warning biomarkers for type 4 cardio-renal syndrome based on bioinformatics analysis and secreted proteins.Scientific reports · 2025Article
- Targeting STING to disrupt macrophage-mediated adhesion in encapsulating peritoneal sclerosis.Communications biology · 2025Article
- Emerging role of the cGAS-STING pathway in cardiovascular diseases: biologic function, mechanisms and targeted therapy.Molecular medicine (Cambridge, Mass.) · 2025Review
- Screening of biomarkers for diagnosing chronic kidney disease and heart failure with preserved ejection fraction through bioinformatics analysis.Biochemistry and biophysics reports · 2025Article
- Mechanisms of mitochondrial damage-associated molecular patterns associated with inflammatory response in cardiovascular diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- The immunology of diabetic cardiomyopathy.Frontiers in endocrinology · 2025Review
- Highly differentiated T cells link systemic and vascular inflammation in a mouse model of recurrent psoriasis.Frontiers in immunology · 2025Article
- Myofibroblast-derived exosomes enhance macrophages to myofibroblasts transition and kidney fibrosis.Renal failure · 2024Article
- Cytotoxic T cells drive doxorubicin-induced cardiac fibrosis and systolic dysfunction.Nature cardiovascular research · 2024Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aims: Cardiac fibrosis is central to heart failure (HF), especially HF with preserved ejection fraction (HFpEF), often caused by hypertension. Despite fibrosis causing diastolic dysfunction and impaired electrical conduction, responsible for arrhythmia-induced sudden cardiac death, the mechanisms are poorly defined and effective therapies are lacking. Here we show that crosstalk between cardiac cytotoxic memory CD8+ T cells and overly stressed cardiomyocytes is essential for development of non-ischemic hypertensive cardiac fibrosis. Methods and results: CD8 T cell depletion in hypertensive mice, strongly attenuated CF, reduced cardiac apoptosis and improved ventricular relaxation. Interaction between cytotoxic memory CD8+ T cells and overly stressed cardiomyocytes is highly dependent on the CD8+ T cells expressing the innate stress-sensing receptor NKG2D and stressed cardiomyocytes expressing the NKG2D activating ligand RAE-1. The interaction between NKG2D and RAE-1 results in CD8+ T cell activation, release of perforin, cardiomyocyte apoptosis, increased numbers of TGF-β1 expressing macrophages and fibrosis. Deleting NKG2D or perforin from CD8+ T cells greatly attenuates these effects. Activation of the cytoplasmic DNA-STING-TBK1-IRF3 signaling pathway in overly stressed cardiomyocytes is responsible for elevating RAE-1 and MCP-1, a macrophage attracting chemokine. Inhibiting STING activation greatly attenuates cardiomyocyte RAE-1 expression, the cardiomyocyte apoptosis, TGF-β1 and fibrosis. Conclusion: Our data highlight a novel pathway by which CD8 T cells contribute to an early triggering mechanism in CF development; preventing CD8+ T cell activation by inhibiting the cardiomyocyte RAE-1-CD8+ T cell-NKG2D axis holds promise for novel therapeutic strategies to limit hypertensive cardiac fibrosis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.