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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Diny, NL; Hou, X; Barin, JG; Chen, G; Talor, MV; Schaub, J; Russell, SD; Klingel, K; Rose, NR; ─îiháková, D

Published Date

  • December 2016

Published In

Volume / Issue

  • 46 / 12

Start / End Page

  • 2749 - 2760

PubMed ID

  • 27621211

Pubmed Central ID

  • 27621211

Electronic International Standard Serial Number (EISSN)

  • 1521-4141

Digital Object Identifier (DOI)

  • 10.1002/eji.201646557

Language

  • eng

Conference Location

  • Germany