Cited by 181Cardiac Fibrosis and RemodelingViral Infections and Immunology ResearchCardiomyopathy and Myosin Studies
Cardiac fibroblasts mediate IL-17A–driven inflammatory dilated cardiomyopathy
Open accessWu, Lei, Ong, SuFey, Talor, Monica V., Barin, Jobert G., Baldeviano, G. Christian, Kass, David A., Bedja, Djahida, Zhang, Hao +5 more·2014·Journal of Experimental Medicine
DOI 10.1084/jem.20132126PMC PMC4076595
Abstract
Inflammatory dilated cardiomyopathy (DCMi) is a major cause of heart failure in individuals below the age of 40. We recently reported that IL-17A is required for the development of DCMi. We show a novel pathway connecting IL-17A, cardiac fibroblasts (CFs), GM-CSF, and heart-infiltrating myeloid cells with the pathogenesis of DCMi. Il17ra−/− mice were protected from DCMi, and this was associated with significantly diminished neutrophil and Ly6Chi monocyte/macrophage (MO/MΦ) cardiac infiltrates. Depletion of Ly6Chi MO/MΦ also protected mice from DCMi. Mechanistically, IL-17A stimulated CFs to produce key chemokines and cytokines that are critical downstream effectors in the recruitment and differentiation of myeloid cells. Moreover, IL-17A directs Ly6Chi MO/MΦ in trans toward a more proinflammatory phenotype via CF-derived GM-CSF. Collectively, this IL-17A–fibroblast–GM-CSF–MO/MΦ axis could provide a novel target for the treatment of DCMi and related inflammatory cardiac diseases.
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In mice with EAM, IL-17A secreted by pathogenic T cells directly stimulates fibroblasts, promoting production of cytokines and chemokines that actively recruit and differentiate inflammatory monocytes.
“In mice with EAM, IL-17A secreted by pathogenic T cells directly stimulates fibroblasts, promoting the production of cytokines and chemokines that actively recruit and differentiate inflammatory monocytes”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [77]
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- Authors
- Wu, L., Ong, S., Talor, M. V., Barin, J. G., Baldeviano, G. C., Kass, D. A., Bedja, D., Zhang, H., Sheikh, A., Margolick, J. B., Iwakura, Y., Rose, N. R., & Čiháková, D.
- Affiliations
- Johns Hopkins University (US)
- United States Naval Medical Research Unit SOUTH (PE)
- Research Institute for Biomedical Sciences, Tokyo University of Science (JP)
- ORCID
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2014-06-16
- Volume
- 211
- Issue
- 7
- Pages
- 1449-1464
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC4076595
- OpenAlex
- W2083467607
- Cited by
- 181
- References
- 51
- Citations by year
- 2026: 12 · 2025: 13 · 2024: 21 · 2023: 20 · 2022: 13 · 2021: 15 · 2020: 15 · 2019: 20 · 2018: 17 · 2017: 14 · 2016: 12 · 2015: 8 · 2014: 1
- FWCI
- 8.02
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- Amgen
- Johns Hopkins University
- Children's Cardiomyopathy Foundation
- National Institutes of Health (UL1TR001079)
- National Heart, Lung, and Blood Institute (R01HL136586, R01HL113008, R01HL118183)
- National Cancer Institute (R01CA289729)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Viral Infections and Immunology Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiomyopathy and Myosin Studies
- Keywords
- inflammatory dilated cardiomyopathy, IL-17A, cardiac fibroblasts, GM-CSF, myeloid cells, neutrophils, chemokines, cytokines, heart failure, myeloid cell recruitment, pro-inflammatory phenotype, therapeutic target
- MeSH terms
- Animals, Cardiomyopathy, Dilated, Fibroblasts, Macrophages, Mice, Inbred BALB C, Monocytes, Myocardium, Neutrophils, Granulocyte-Macrophage Colony-Stimulating Factor, Mice, Knockout, Interleukin-17, Neutrophil Infiltration, Mice
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