ArticleThe Journal of clinical investigation2011
Impaired thymic tolerance to α-myosin directs autoimmunity to the heart in mice and humans.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 140 papers, 2 of them syntheses that pooled it.
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Who cites it
140 citing papers in PubMed, 2 syntheses or guidelines pooled it, 212 citations in OpenAlex.
- Thymus alterations and susceptibility to immune checkpoint inhibitor myocarditis.Nature medicine · 2023Pooled it
- Brazilian Society of Cardiology Guideline on Myocarditis - 2022.Arquivos brasileiros de cardiologia · 2022Guideline
- Glycemic Control, Cardiac Autoimmunity, and Long-Term Risk of Cardiovascular Disease in Type 1 Diabetes Mellitus.Circulation · 2019Trial
- Heart-specific T cell responses: from antigens to disease mechanisms.Nature reviews. Cardiology · 2026Review
- HnRNPK suppresses macrophage-driven inflammation in autoimmune myocarditis by restraining NCF1-dependent oxidized phospholipid signaling and ferroptosis-related changes.Redox biology · 2026Article
- Myocardial injury in systemic lupus erythematosus and lupus nephritis: a silent threat.Clinical kidney journal · 2026Review
- The Cardio-Onco-Immune Axis: immunopathological mechanisms in the cardiac microenvironment of checkpoint inhibitor-induced myocarditis.Acta pharmacologica Sinica · 2026Review
- β1 Autoantibodies Stimulate T Cells to Become Cardiotoxic.JACC. Basic to translational science · 2026Article
- Central T cell tolerance from sparse peptide sampling.Science advances · 2026Article
- Myocardial Immune Niches in Homeostasis and Inflammation.Immunological reviews · 2026Review
- Coronary Microvascular Dysfunction in Stress Cardiomyopathy: At the Heart of the Problem.Life (Basel, Switzerland) · 2026Review
- T cells in acute and chronic myocarditis: from diagnosis to treatment.European heart journal · 2026Review
- T Cell Receptor Repertoires Across the Continuum of Vascular, Myocardial, and Age-Related Diseases.Immunological reviews · 2026Review
- Immune checkpoint inhibitor-induced cardiotoxicity: from immune mechanisms to clinical surveillance and targeted therapies.Frontiers in cardiovascular medicine · 2026Review
- Understanding immune checkpoint inhibitors-related myocarditis: Mechanisms and targeted therapeutic pathways.Theranostics · 2026Review
- Cardioprotective Effect of Metformin Treatment in Mouse Model of Experimental Autoimmune Myocarditis.Cardiovascular therapeutics · 2026Article
- Key immune checkpoint inhibitor-associated toxicities: from molecular mechanisms to clinical management.Frontiers in pharmacology · 2026Review
- From tumor immunotherapy to myocardial injury: A mechanistic discussion of immune checkpoint inhibitor‑related myocarditis (Review).Molecular medicine reports · 2025Review
- A review of immune checkpoint inhibitor-associated myocarditis: Epidemiology, pathogenesis, and biomarkers.Human vaccines & immunotherapeutics · 2025Review
- Bulk RNAseq Analysis of Cardiac Myosin-Specific CD4Biomedicines · 2025Article
80 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
Autoimmunity has long been linked to myocarditis and its sequela, dilated cardiomyopathy, the leading causes of heart failure in young patients. However, the underlying mechanisms are poorly defined, with most clinical investigations focused on humoral autoimmunity as the target for intervention. Here, we show that the α-isoform of myosin heavy chain (α-MyHC, which is encoded by the gene Myh6) is the pathogenic autoantigen for CD4+ T cells in a spontaneous mouse model of myocarditis. Further, we found that Myh6 transcripts were absent in mouse medullary thymic epithelial cells (mTECs) and peripheral lymphoid stromal cells, which have been implicated in mediating central and peripheral T cell tolerance, respectively. Transgenic expression of α-MyHC in thymic epithelium conferred tolerance to cardiac myosin and prevented myocarditis, demonstrating that α-MyHC is a primary autoantigen in this disease process. Remarkably, we found that humans also lacked α-MyHC in mTECs and had high frequencies of α-MyHC-specific T cells in peripheral blood, with markedly augmented T cell responses to α-MyHC in patients with myocarditis. Since α-MyHC constitutes a small fraction of MyHC in human heart, these findings challenge the longstanding notion that autoimmune targeting of MyHC is due to its cardiac abundance and instead suggest that it is targeted as a result of impaired T cell tolerance mechanisms. These results thus support a role for T cell-specific therapies for myocarditis.
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Registered trials
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.