Deleterious effect of the IL-23/IL-17A axis and γδT cells on left ventricular remodeling after myocardial infarction.

Xiaoxiang Yan, Takashi Shichita, Yoshinori Katsumata, Tomohiro Matsuhashi, Hideyuki Ito, Kentaro Ito, Atsushi Anzai, Jin Endo, Yuichi Tamura, Kensuke Kimura, Jun Fujita, Ken Shinmura, Weifeng Shen, Akihiko Yoshimura, Keiichi Fukuda, Motoaki Sano

研究成果: Article

67 引用 (Scopus)

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Left ventricular (LV) remodeling leads to chronic heart failure and is a main determinant of morbidity and mortality after myocardial infarction (MI). At the present time, therapeutic options to prevent LV remodeling are limited. We created a large MI by permanent ligation of the coronary artery and identified a potential link between the interleukin (IL)-23/IL-17A axis and γδT cells that affects late-stage LV remodeling after MI. Despite the finsinf that infarct size 24 hours after surgery was similar to that in wild-type mice, a deficiency in IL-23, IL-17A, or γδT cells improved survival after 7 days, limiting infarct expansion and fibrosis in noninfarcted myocardium and alleviating LV dilatation and systolic dysfunction on day 28 post-MI. M(1) macrophages and neutrophils were the major cellular source of IL-23, whereas >90% of IL-17A-producing T cells in infarcted heart were CD4(-) TCRγδ(+) (γδT) cells. Toll-like receptor signaling and IL-1β worked in concert with IL-23 to drive expansion and IL-17A production in cardiac γδT cells, whereas the sphingosine-1-phosphate receptor and CCL20/CCR6 signaling pathways mediated γδT cell recruitment into infarcted heart. IL-17A was not involved in the acute inflammatory response, but it functioned specifically in the late remodeling stages by promoting sustained infiltration of neutrophils and macrophages, stimulating macrophages to produce proinflammatory cytokines, aggravating cardiomyocyte death, and enhancing fibroblast proliferation and profibrotic gene expression. The IL-23/IL-17A immune axis and γδT cells are potentially promising therapeutic targets after MI to prevent progression to end-stage dilated cardiomyopathy.

元の言語English
ページ(範囲)e004408
ジャーナルUnknown Journal
1
発行部数5
DOI
出版物ステータスPublished - 2012 10

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ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

これを引用

Yan, X., Shichita, T., Katsumata, Y., Matsuhashi, T., Ito, H., Ito, K., Anzai, A., Endo, J., Tamura, Y., Kimura, K., Fujita, J., Shinmura, K., Shen, W., Yoshimura, A., Fukuda, K., & Sano, M. (2012). Deleterious effect of the IL-23/IL-17A axis and γδT cells on left ventricular remodeling after myocardial infarction. Unknown Journal, 1(5), e004408. https://doi.org/10.1161/JAHA.112.004408