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Roles and Mechanisms of TGR5 in the Modulation of CD4+ T Cell Functions in Myocardial Infarction

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Abstract

Bile acid receptor TGR5 has been proved to play protective roles in the process of myocardial infarction (MI). Recently, we found spleen weight of Tgr5+/+ mice was increased at 7-day post-MI but not in Tgr5−/− mice. Since the spleen is one of the main resources of immune and inflammatory cells post-MI, we conducted flow cytometry analysis of multiple immune cells in the heart post-MI. It showed the recruitment of CD4+ T cells and CD8+ T cells was continuously more in the heart of Tgr5−/− mice post-MI until 7 days after MI. Furthermore, CD4-specific TGR5 depletion mice exhibited aggravated ischemic injury. The mRNA expressions of the markers of Th1 and Treg were upregulated in the heart of Tgr5−/− mice at 7-day post-MI. These results suggested TGR5 modulates CD4+ T cell functions and subsets distribution in the heart, and plays protective roles in myocardial infarction.

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Acknowledgements

We greatly appreciate Professor Changtao Jiang, School of Basic Medical Sciences, Peking University, for providing valuable opinions and suggestions on the study, especially the Tgr5 global deletion mice.

Funding

This work was supported by the National Natural Science Foundation of China (Grant No. 81900315, Grant No. 81625001) and the National Key Research & Development Program of China (Grant No. 2018YFC1312700, Grant No. 2018YFC1312701).

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Author notes

  1. Jiaxing Wang and Tan Xu contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing, 100191, China

    Jiaxing Wang, Tan Xu & Ming Xu

  2. NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptide, Peking University Third Hospital, Beijing, 100191, China

    Jiaxing Wang, Tan Xu & Ming Xu

  3. Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Peking University Third Hospital, Beijing, 100191, China

    Jiaxing Wang, Tan Xu & Ming Xu

  4. Beijing Key Laboratory of Cardiovascular Receptors Research, Peking University Third Hospital, Beijing, 100191, China

    Jiaxing Wang, Tan Xu & Ming Xu

  5. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China

    Ming Xu

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All the authors contributed to the study’s conception and design. Material preparation, data collection, and analysis were performed by Jiaxing Wang and Tan Xu. The first draft of the manuscript was written by Jiaxing Wang and all the authors commented on previous versions of the manuscript. All the authors read and approved the final manuscript.

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Correspondence to Ming Xu.

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No human studies were carried out by the authors for this article. This study conformed to the Guidelines for the Care and Use of Laboratory Animals published by the US National Institutes of Health and was approved by the Institutional Animal Care and Use Committee at Peking University Health Science Center (LA2019138, LA2021363).

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Associate Editor Junjie Xiao oversaw the review of this article

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Wang, J., Xu, T. & Xu, M. Roles and Mechanisms of TGR5 in the Modulation of CD4+ T Cell Functions in Myocardial Infarction. J. of Cardiovasc. Trans. Res. 15, 350–359 (2022). https://doi.org/10.1007/s12265-021-10164-2

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