The DOI matches its Crossref record; 85 of the 88 references it cites were found in a registry or an index.
Cardiac myosin-Th17 responses promote heart failure in human myocarditis
Open accessAbstract
In human myocarditis and its sequela dilated cardiomyopathy (DCM), the mechanisms and immune phenotype governing disease and subsequent heart failure are not known. Here, we identified a Th17 cell immunophenotype of human myocarditis/DCM with elevated CD4 + IL17 + T cells and Th17-promoting cytokines IL-6, TGF-β, and IL-23 as well as GM-CSF–secreting CD4 + T cells. The Th17 phenotype was linked with the effects of cardiac myosin on CD14 + monocytes, TLR2, and heart failure. Persistent heart failure was associated with high percentages of IL-17–producing T cells and IL-17–promoting cytokines, and the myocarditis/DCM phenotype included significantly low percentages of FOXP3 + Tregs, which may contribute to disease severity. We demonstrate a potentially novel mechanism in human myocarditis/DCM in which TLR2 peptide ligands from human cardiac myosin stimulated exaggerated Th17-related cytokines including TGF-β, IL-6, and IL-23 from myocarditic CD14 + monocytes in vitro, and an anti-TLR2 antibody abrogated the cytokine response. Our translational study explains how an immune phenotype may be initiated by cardiac myosin TLR ligand stimulation of monocytes to generate Th17-promoting cytokines and development of pathogenic Th17 cells in human myocarditis and heart failure, and provides a rationale for targeting IL-17A as a therapeutic option.
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“IL-1 β also increases serum and cardiac IL-6 levels that are needed to drive Th17 responses, which also promote fibrosis and progression to DCM and heart failure in patients with myocarditis and in animal models. 36,165,172-174”
From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [36]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Following infection, viruses and heart antigens resulting from cardiac damage trigger innate immune responses by engaging TLRs, potentially leading to the activation of antiviral adaptive immunity and B cells and T cells targeting cardiac autoantigens”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [64]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Recent studies implemented pathogenic T cells as potential diagnostic or therapeutic targets for autoimmune myocarditis including ICI myocarditis, demonstrating promising outcomes at both clinical and preclinical levels. 51,64,238,254,260,311,312”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [64]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Subsequent investigations revealed the presence of these autoreactive T cells in the peripheral blood mononuclear cells of patients with myocarditis”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [64]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“in patients with myocarditis, the number of Th17 cells was increased in the PBMC and myocardial tissue, and Th17-type cytokine levels were associated with heart failure and nonrecovery conditions”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [64]
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“a decreased number of circulating regulatory T cells were found in patients with myocarditis, and adoptive transfer of CD4 + T cells with regulatory T-cell depletion induced fatal myocarditis in mice”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [64]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In patients with myocarditis or idiopathic DCM who tested negative for specific viruses, the presence of circulating Th17 cells specific for cardiac myosin in the blood has been reported, along with a reduced number of regulatory T cells. 64,238,311”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [64]
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Citations
Cites
1 retracted
Zhu, H., Lou, C., & Liu, P. (2015) · Virology Journal · doi:10.1186/s12985-015-0418-x · Cited by 31
RetractedBettelli, E., Carrier, Y., Gao, W., Korn, T., Strom, T. B., Oukka, M., Weiner, H. L., & Kuchroo, V. K. (2006) · Nature · doi:10.1038/nature04753 · Cited by 6,992
Korn, T., Bettelli, E., Oukka, M., & Kuchroo, V. K. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132710 · Cited by 4,873
Caforio, A. L. P., Pankuweit, S., Arbustini, E., Basso, C., Gimeno-Blanes, J., Felix, S. B., Fu, M., Heliö, T., Heymans, S., Jahns, R., et al. (2013) · European Heart Journal · doi:10.1093/eurheartj/eht210 · Cited by 3,479
Transforming growth factor-β induces development of the TH17 lineage
Mangan, P. R., Harrington, L. E., O'Quinn, D. B., Helms, W. S., Bullard, D. C., Elson, C. O., Hatton, R. D., Wahl, S. M., Schoeb, T. R., & Weaver, C. T. (2006) · Nature · doi:10.1038/nature04754 · Cited by 3,087
Cua, D. J., Sherlock, J., Chen, Y., Murphy, C. A., Joyce, B., Seymour, B., Lucian, L., To, W., Kwan, S., Churakova, T., et al. (2003) · Nature · doi:10.1038/nature01355 · Cited by 2,906
Transcriptional regulation of macrophage polarization: enabling diversity with identity
Lawrence, T., & Natoli, G. (2011) · Nature Reviews Immunology · doi:10.1038/nri3088 · Cited by 2,284
TGF-β-induced Foxp3 inhibits TH17 cell differentiation by antagonizing RORγt function
Zhou, L., Lopes, J. E., Chong, M. M. W., Ivanov, I. I., Min, R., Victora, G. D., Shen, Y., Du, J., Rubtsov, Y. P., Rudensky, A. Y., et al. (2008) · Nature · doi:10.1038/nature06878 · Cited by 1,928
Phenotypic and functional features of human Th17 cells
Annunziato, F., Cosmi, L., Santarlasci, V., Maggi, L., Liotta, F., Mazzinghi, B., Parente, E., Filì, L., Ferri, S., Frosali, F., et al. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070663 · Cited by 1,861
Acosta-Rodriguez, E. V., Napolitani, G., Lanzavecchia, A., & Sallusto, F. (2007) · Nature Immunology · doi:10.1038/ni1496 · Cited by 1,857
Research works printed but not linked: 2
- Smith, 1991, Myosin-induced acute myocarditis is a T cell mediated disease, J Immunol, 147, 2141, 10.4049/jimmunol.147.7.2141 · DOI
- 10.1161/CIRCRESAHA.109.213157 · DOI · Paper page
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Metadata
- Authors
- Myers, J. M., Cooper, L. T., Kem, D. C., Stavrakis, S., Kosanke, S. D., Shevach, E. M., Fairweather, D., Stoner, J. A., Cox, C. J., & Cunningham, M. W.
- Affiliations
- University of Oklahoma Health Sciences Center (US)
- Mayo Clinic in Florida (US)
- Department of Medicine/Endocrinology,
- Medicine/Cardiology, and
- National Institutes of Health (US)
- Johns Hopkins University (US)
- Corresponding author
- Cox, Carol J.
- Cunningham, Madeleine W.
- ORCID
- Venue
- JCI Insight
- Published
- 2016-06-16
- Volume
- 1
- Issue
- 9
- ISSN
- 2379-3708 (ISSN-L)
- PMC
- PMC4924810
- OpenAlex
- W2434470226
- Cited by
- 230
- References
- 88
- Citations by year
- 2026: 22 · 2025: 26 · 2024: 33 · 2023: 34 · 2022: 24 · 2021: 29 · 2020: 24 · 2019: 16 · 2018: 12 · 2017: 9 · 2016: 1
- FWCI
- 10.43
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- JCI Insight (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association (U54GM104938)
- University of Oklahoma
- University of Oklahoma Health Sciences Center
- National Heart, Lung, and Blood Institute (R01HL135165, R56HL056267, R01HL111938, R01HL056267, R37HL035280)
- National Institute of General Medical Sciences (U54GM104938)
- National Institute of Allergy and Infectious Diseases (T32AI007633)
- National Institute of Environmental Health Sciences (R21ES024414)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Viral Infections and Immunology Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
- Keywords
- myocarditis, dilated cardiomyopathy, heart failure, Th17 cells, cardiac myosin, TLR2, CD14+ monocytes, IL-17, interleukin-6, TGF-beta, IL-23, GM-CSF, regulatory T cells, Foxp3, autoimmunity
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