GM-CSF primes cardiac inflammation in a mouse model of Kawasaki disease
- Author(s)
- Stock, AT; Hansen, JA; Sleeman, MA; McKenzie, BS; Wicks, IP;
- Details
- Publication Year 2016-09-05,Volume 213,Issue #10,Page 1983-98
- Journal Title
- J Exp Med
- Publication Type
- Journal Article
- Abstract
- Kawasaki disease (KD) is the leading cause of pediatric heart disease in developed countries. KD patients develop cardiac inflammation, characterized by an early infiltrate of neutrophils and monocytes that precipitates coronary arteritis. Although the early inflammatory processes are linked to cardiac pathology, the factors that regulate cardiac inflammation and immune cell recruitment to the heart remain obscure. In this study, using a mouse model of KD (induced by a cell wall Candida albicans water-soluble fraction [CAWS]), we identify an essential role for granulocyte/macrophage colony-stimulating factor (GM-CSF) in orchestrating these events. GM-CSF is rapidly produced by cardiac fibroblasts after CAWS challenge, precipitating cardiac inflammation. Mechanistically, GM-CSF acts upon the local macrophage compartment, driving the expression of inflammatory cytokines and chemokines, whereas therapeutically, GM-CSF blockade markedly reduces cardiac disease. Our findings describe a novel role for GM-CSF as an essential initiating cytokine in cardiac inflammation and implicate GM-CSF as a potential target for therapeutic intervention in KD.
- Publisher
- Rockefeller Uni Press
- Research Division(s)
- Inflammation
- PubMed ID
- 27595596
- Link To PubMed Central Version
- https://www-ncbi-nlm-nih-gov/pmc/articles/PMC5030799/
- Publisher's Version
- https://doi.org/10.1084/jem.20151853
- NHMRC Grants
- NHMRC/1023407, NHMRC/0123462,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2016-10-03 03:38:08
Last Modified: 2017-08-21 08:33:20