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IL-1-Activated Inflammatory Cardiac Fibroblasts Exacerbate Acute Coxsackievirus B3 Myocarditis

David S Elias1, Wonyoung Jo1, Monica V Talor1

  • 1Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.

JACC. Basic to Translational Science
|July 23, 2026
PubMed

Insights

Inflammatory fibroblasts (IFs) drive viral myocarditis by producing chemokines, not profibrotic genes. Targeting IL-1 signaling in these fibroblasts significantly reduces heart inflammation, offering a potential therapeutic strategy for this dangerous heart condition.

Area of Science:

  • Cardiology
  • Immunology
  • Fibroblast Biology

Background:

  • Acute viral myocarditis is a severe heart condition often triggered by viral infections like coxsackievirus B3 (CVB3).
  • The role of inflammatory fibroblasts (IFs) in the pathogenesis of viral myocarditis is not fully understood.
  • Identifying specific molecular pathways driving IF activation is crucial for therapeutic development.

Purpose of the Study:

  • To investigate the kinetics and functional role of inflammatory fibroblasts (IFs) in acute viral myocarditis.
  • To identify key molecular signals that activate IFs during myocarditis.
  • To evaluate the therapeutic potential of targeting fibroblast-specific signaling pathways.

Main Methods:

  • Utilized CCL2-mCherry reporter mice to track IFs during CVB3-induced myocarditis.
  • Analyzed chemokine and gene expression profiles of IFs.
  • Generated and studied PDGFRαcreIL1r1fl/fl mice with fibroblast-specific deletion of IL-1 receptor signaling.
  • Examined endomyocardial biopsies from human patients.

Main Results:

  • IFs exhibited peak activity on day 3 of myocarditis, producing Th1, Th2, and Th17 chemokines.
  • Interleukin-1 beta (IL-1β) was identified as a potent activator of IFs.
  • Targeted deletion of IL-1 signaling in fibroblasts reduced cardiac inflammation by 45%, decreasing monocytes, T cells, and NK cells, without impacting viral clearance.
  • IFs were confirmed in human myocardial biopsies.

Conclusions:

  • Fibroblast-specific IL-1 signaling is a critical driver of cardiac inflammation in viral myocarditis.
  • IFs contribute to myocarditis pathogenesis through chemokine production rather than profibrotic activity.
  • Targeting fibroblast IL-1 signaling represents a promising therapeutic strategy for viral myocarditis.
Keywords:
IL-1inflammatory fibroblastsplasticityviral myocarditis

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