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Xu JY, Xiong YY, Tang RJ, et al. Interleukin-5-induced eosinophil population improves cardiac function after myocardial infarction. Cardiovasc Res. 2021;doi: 10.1093/cvr/cvab237.
Xu, J. Y., Xiong, Y. Y., Tang, R. J., Jiang, W. Y., Ning, Y., Gong, Z. T., Huang, P. S., Chen, G. H., Xu, J., Wu, C. X., Hu, M. J., Xu, J., Xu, Y., Huang, C. R., Jin, C., Lu, X. T., Qian, H. Y., Li, X. D., & Yang, Y. J. (2021). Interleukin-5-induced eosinophil population improves cardiac function after myocardial infarction. Cardiovascular research, . https://doi.org/10.1093/cvr/cvab237
Xu, Jun-Yan, et al. "Interleukin-5-induced eosinophil population improves cardiac function after myocardial infarction." Cardiovascular research vol. (2021). doi: https://doi.org/10.1093/cvr/cvab237
Xu JY, Xiong YY, Tang RJ, Jiang WY, Ning Y, Gong ZT, Huang PS, Chen GH, Xu J, Wu CX, Hu MJ, Xu J, Xu Y, Huang CR, Jin C, Lu XT, Qian HY, Li XD, Yang YJ. Interleukin-5-induced eosinophil population improves cardiac function after myocardial infarction. Cardiovasc Res. 2021 Jul 14; doi: 10.1093/cvr/cvab237. Epub 2021 Jul 14. PMID: 34259869.
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Cardiovasc Res. 2021 Jul 14; doi: 10.1093/cvr/cvab237. Epub 2021 Jul 14.

Interleukin-5-induced eosinophil population improves cardiac function after myocardial infarction.

Cardiovascular research

Jun-Yan Xu, Yu-Yan Xiong, Rui-Jie Tang, Wen-Yang Jiang, Yu Ning, Zhao-Ting Gong, Pei-Sen Huang, Gui-Hao Chen, Jun Xu, Chun-Xiao Wu, Meng-Jin Hu, Jing Xu, Yi Xu, Cun-Rong Huang, Chen Jin, Xiao-Tong Lu, Hai-Yan Qian, Xiang-Dong Li, Yue-Jin Yang

Affiliations

  1. State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No.167 Bei Li Shi Road, Xicheng District, Beijing, 100037, People's Republic of China.
  2. Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
  3. Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou, China.
  4. National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, People's Republic of China.

PMID: 34259869 DOI: 10.1093/cvr/cvab237

Abstract

AIMS: Interleukin (IL)-5 mediates the development of eosinophils (EOS) that are essential for tissue post-injury repair. It remains unknown whether IL-5 plays a role in heart repair after myocardial infarction (MI). This study aims to test whether IL-5-induced EOS population promotes the healing and repair process post-MI and to reveal the underlying mechanisms.

METHOD AND RESULTS: MI was induced by permanent ligation of the left anterior descending coronary artery in wild-type C57BL/6 mice. Western blot and real-time polymerase chain reaction revealed elevated expression of IL-5 in the heart at 5 days post-MI. Immunohistostaining indicated that IL-5 was secreted mainly from macrophages and type 2 innate lymphoid cells in the setting of experimental MI. External supply of recombinant mouse IL-5 (20 min, 1 day, and 2 days after MI surgery) reduced the infarct size and increased ejection fraction and angiogenesis in the border zone. A significant expansion of EOS was detected in both the peripheral blood and infarcted myocardium after IL-5 administration. Pharmacological depletion of EOS by TRFK5 pretreatment muted the beneficial effects of IL-5 in MI mice. Mechanistic studies demonstrated that IL-5 increased the accumulation of CD206+ macrophages in infarcted myocardium at 7 days post-MI. In vitro co-culture experiments showed that EOS shifted bone marrow-derived macrophage polarization towards the CD206+ phenotypes. This activity of EOS was abolished by IL-4 neutralizing antibody, but not IL-10 or IL-13 neutralization. Western blot analyses demonstrated that EOS promoted the macrophage downstream signal transducer and activator of transcription 6 (STAT6) phosphorylation.

CONCLUSION: IL-5 facilitates the recovery of cardiac dysfunction post-MI by promoting EOS accumulation and subsequent CD206+ macrophage polarization via the IL-4/STAT6 axis.

TRANSLATIONAL PERSPECTIVE: Accumulating evidence suggests that modulation of innate and adaptive immune responses is a promising therapeutic strategy for myocardial infarction. In this study, we demonstrate that IL-5 exerts cardioprotective effects on infarcted myocardium by promoting eosinophil accumulation and subsequent CD206+ macrophage polarization via the IL-4/STAT6 axis. Hence, regulation of cardiac IL-5 level or eosinophil count may become a therapeutic approach for post-myocardial infarction cardiac repair in humans.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions please email: [email protected].

Keywords: Myocardial infarction; alternatively activated macrophage; eosinophil; interleukin-4; interleukin-5

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