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Deleterious Effect of the IL-23/IL-17A Axis and γδT Cells on Left Ventricular Remodeling After Myocardial Infarction

BACKGROUND: 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. METHODS AND RESULTS: We created a large MI by permanent li...

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Autores principales: Yan, Xiaoxiang, Shichita, Takashi, Katsumata, Yoshinori, Matsuhashi, Tomohiro, Ito, Hideyuki, Ito, Kentaro, Anzai, Atsushi, Endo, Jin, Tamura, Yuichi, Kimura, Kensuke, Fujita, Jun, Shinmura, Ken, Shen, Weifeng, Yoshimura, Akihiko, Fukuda, Keiichi, Sano, Motoaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3541626/
https://www.ncbi.nlm.nih.gov/pubmed/23316306
http://dx.doi.org/10.1161/JAHA.112.004408
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author Yan, Xiaoxiang
Shichita, Takashi
Katsumata, Yoshinori
Matsuhashi, Tomohiro
Ito, Hideyuki
Ito, Kentaro
Anzai, Atsushi
Endo, Jin
Tamura, Yuichi
Kimura, Kensuke
Fujita, Jun
Shinmura, Ken
Shen, Weifeng
Yoshimura, Akihiko
Fukuda, Keiichi
Sano, Motoaki
author_facet Yan, Xiaoxiang
Shichita, Takashi
Katsumata, Yoshinori
Matsuhashi, Tomohiro
Ito, Hideyuki
Ito, Kentaro
Anzai, Atsushi
Endo, Jin
Tamura, Yuichi
Kimura, Kensuke
Fujita, Jun
Shinmura, Ken
Shen, Weifeng
Yoshimura, Akihiko
Fukuda, Keiichi
Sano, Motoaki
author_sort Yan, Xiaoxiang
collection PubMed
description BACKGROUND: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.
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spelling pubmed-35416262013-01-11 Deleterious Effect of the IL-23/IL-17A Axis and γδT Cells on Left Ventricular Remodeling After Myocardial Infarction Yan, Xiaoxiang Shichita, Takashi Katsumata, Yoshinori Matsuhashi, Tomohiro Ito, Hideyuki Ito, Kentaro Anzai, Atsushi Endo, Jin Tamura, Yuichi Kimura, Kensuke Fujita, Jun Shinmura, Ken Shen, Weifeng Yoshimura, Akihiko Fukuda, Keiichi Sano, Motoaki J Am Heart Assoc Original Research BACKGROUND: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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. Blackwell Publishing Ltd 2012-10-25 /pmc/articles/PMC3541626/ /pubmed/23316306 http://dx.doi.org/10.1161/JAHA.112.004408 Text en © 2012 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley-Blackwell. http://creativecommons.org/licenses/by/2.5/ This is an Open Access article under the terms of the Creative Commons Attribution Noncommercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Research
Yan, Xiaoxiang
Shichita, Takashi
Katsumata, Yoshinori
Matsuhashi, Tomohiro
Ito, Hideyuki
Ito, Kentaro
Anzai, Atsushi
Endo, Jin
Tamura, Yuichi
Kimura, Kensuke
Fujita, Jun
Shinmura, Ken
Shen, Weifeng
Yoshimura, Akihiko
Fukuda, Keiichi
Sano, Motoaki
Deleterious Effect of the IL-23/IL-17A Axis and γδT Cells on Left Ventricular Remodeling After Myocardial Infarction
title Deleterious Effect of the IL-23/IL-17A Axis and γδT Cells on Left Ventricular Remodeling After Myocardial Infarction
title_full Deleterious Effect of the IL-23/IL-17A Axis and γδT Cells on Left Ventricular Remodeling After Myocardial Infarction
title_fullStr Deleterious Effect of the IL-23/IL-17A Axis and γδT Cells on Left Ventricular Remodeling After Myocardial Infarction
title_full_unstemmed Deleterious Effect of the IL-23/IL-17A Axis and γδT Cells on Left Ventricular Remodeling After Myocardial Infarction
title_short Deleterious Effect of the IL-23/IL-17A Axis and γδT Cells on Left Ventricular Remodeling After Myocardial Infarction
title_sort deleterious effect of the il-23/il-17a axis and γδt cells on left ventricular remodeling after myocardial infarction
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3541626/
https://www.ncbi.nlm.nih.gov/pubmed/23316306
http://dx.doi.org/10.1161/JAHA.112.004408
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