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Cited by 70Viral Infections and Immunology ResearchEosinophilic Disorders and SyndromesCardiac Fibrosis and Remodeling

Macrophages and cardiac fibroblasts are the main producers of eotaxins and regulate eosinophil trafficking to the heart

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Diny, Nicola L., Hou, Xuezhou, Barin, Jobert G., Chen, Guobao, Talor, Monica V., Schaub, Julie, Russell, Stuart D., Klingel, Karin +2 more·2016·European Journal of Immunology
DOI 10.1002/eji.201646557PMC PMC5404278
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Abstract

Cardiac manifestations are a major cause of morbidity and mortality in patients with eosinophil‐associated diseases. Eosinophils are thought to play a pathogenic role in myocarditis. We investigated the pathways that recruit eosinophils to the heart using a model of eosinophilic myocarditis, in which experimental autoimmune myocarditis (EAM) is induced in IFNγ −/− IL‐17A −/− mice. Two conditions are necessary for efficient eosinophil trafficking to the heart: high eotaxin (CCL11, CCL24) expression in the heart and expression of the eotaxin receptor CCR3 by eosinophils. We identified cardiac fibroblasts as the source of CCL11 in the heart interstitium. CCL24 is produced by F4/80 + macrophages localized at inflammatory foci in the heart. Expression of CCL11 and CCL24 is controlled by Th2 cytokines, IL‐4 and IL‐13. To determine the relevance of this pathway in humans, we analyzed endomyocardial biopsy samples from myocarditis patients. Expression of CCL11 and CCL26 was significantly increased in eosinophilic myocarditis compared to chronic lymphocytic myocarditis and positively correlated with the number of eosinophils. Thus, eosinophil trafficking to the heart is dependent on the eotaxin‐CCR3 pathway in a mouse model of EAM and associated with cardiac eotaxin expression in patients with eosinophilic myocarditis. Blocking this pathway may prevent eosinophil‐mediated cardiac damage.

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  • The finding of eotaxin production by cardiac macrophages and fibroblasts was confirmed in endomyocardial biopsies from patients with eosinophilic myocarditis.

    “this finding was confirmed in EMB collected from patients with eosinophilic myocarditis.”

    From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [62]

    The Results section reports increased eotaxin expression in endomyocardial biopsies from patients with eosinophilic myocarditis. But the Discussion says the cellular source of eotaxins was not studied in the human heart. The biopsies therefore support the human eotaxin-expression finding, not confirmation that cardiac macrophages and fibroblasts produced it in those patients. (LLM, conf=0.89)

    Experimental — accuracy not yet measured

  • Immunization with cardiac myosin peptide induces severe eosinophilic myocarditis in mutant mice overexpressing IL-5 or lacking both IFNγ and IL-17A, but not in wild-type or control mice.

    “immunization with cardiac myosin peptide induced severe eosinophilic myocarditis in mutant mice skewing toward Th2-type responses by overexpressing IL-5 or genetically deleting both IFNγ and IL-17A but not in wild-type or control mice”

    From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [62]

    The Introduction reports that inducing experimental autoimmune myocarditis in IFN-γ/IL-17A double-knockout mice produces fatal, predominantly eosinophilic myocarditis; Materials and methods identifies the cardiac myosin peptide used for immunization. The Results uses IL-5 transgenic mice as eosinophil donors, not as mice shown to develop eosinophilic myocarditis after immunization. Our copy also does not establish the stated wild-type comparison. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Following immunization, cardiac macrophages and fibroblasts primarily produce eotaxins such as CCL11 and CCL24 to recruit activated inflammatory eosinophils to the heart.

    “following immunization, cardiac macrophages and fibroblasts primarily produced eotaxins such as CCL11 and CCL24 (C-C motif chemokine ligand 24) to recruit activated inflammatory eosinophils to the heart”

    From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [62]

    The Discussion and Results (page numbers unavailable) identify cardiac fibroblasts as the main source of CCL11 and macrophages as a source of CCL24 in immunized mice, and link eotaxin signaling to eosinophil recruitment to the heart. The copy does not establish that the recruited eosinophils were activated, so that qualifier is unsupported. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

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Research works printed but not linked: 54

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Authors
Diny, N. L., Hou, X., Barin, J. G., Chen, G., Talor, M. V., Schaub, J., Russell, S. D., Klingel, K., Rose, N. R., & Čiháková, D.
Affiliations
  • Johns Hopkins University (US)
  • University of Tübingen (DE)
  • Brigham and Women's Hospital (US)
Corresponding author
Čiháková, Daniela
ORCID
Venue
European Journal of Immunology
Publisher
Wiley
Published
2016-10-25
Volume
46
Issue
12
Pages
2749-2760
ISSN
  • 0014-2980 (ISSN-L)
  • 1521-4141
DOI
10.1002/eji.201646557
PMC
PMC5404278
OpenAlex
W2519720623
Cited by
70
References
56
Citations by year
2026: 5 · 2025: 5 · 2024: 7 · 2023: 6 · 2022: 8 · 2021: 7 · 2020: 11 · 2019: 4 · 2018: 9 · 2017: 8
FWCI
5.76
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • European Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (R01HL118183, R01HL113008)
  • American Heart Association (15PRE25400010)
  • Gilead Sciences
  • American Autoimmune Related Diseases Association
  • Deutsche Forschungsgemeinschaft (KL595/2‐3)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Viral Infections and Immunology Research
  • Health Sciences › Medicine › Rheumatology › Eosinophilic Disorders and Syndromes
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
Keywords
eosinophilic myocarditis, eosinophil trafficking, eotaxin, CCL24, CCR3, cardiac fibroblasts, macrophages, Th2 cytokines, IL-4, IL-13, experimental autoimmune myocarditis, eosinophils, endomyocardial biopsy
MeSH terms
Adult, Aged, Animals, Cell Movement, Cells, Cultured, Eosinophils, Female, Fibroblasts, Humans, Interferon-gamma, Macrophages, Male, Mice, Inbred BALB C, Mice, Transgenic, Myocarditis, Myocardium, Mice, Knockout, Nervous System Autoimmune Disease, Experimental, Cardiac Myosins, Mice, Receptors, CCR3, Chemokine CCL11, Chemokine CCL24, Th1-Th2 Balance

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