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

Nicola L. Diny, Xuezhou Hou, Jobert G. Barin, Guobao Chen, Monica V. Talor, Julie Schaub, Stuart D. Russell, Karin Klingel, Noel R. Rose, Daniela Čiháková

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)2749-2760
Number of pages12
JournalEuropean Journal of Immunology
Volume46
Issue number12
DOIs
StatePublished - Dec 1 2016

Keywords

  • Cardiomyopathy
  • Cell trafficking
  • Chemokines
  • Eosinophils
  • Eotaxins
  • Experimental autoimmune myocarditis
  • Inflammation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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