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Regulatory T cells in cardiovascular diseases

Key Points

  • Regulatory T (TREG) cells are involved in immune homeostasis and tolerance, and regulate the progression of autoimmune diseases

  • A reduced number and impaired function of TREG cells might be present in a variety of cardiovascular diseases, including atherosclerosis, hypertension, abdominal aortic aneurysm, myocardial infarction, and heart failure

  • Adoptive transfer of exogenous TREG cells or expansion of endogenous TREG cells effectively attenuates the progression of many cardiovascular diseases

  • The molecular mechanisms mediating the role of TREG cells in the pathogenesis of cardiovascular diseases are still incompletely understood

  • TREG cells might be a promising therapeutic target for cardiovascular disease, and can improve our understanding of the immunomodulatory mechanisms involved in the disease

Abstract

Inflammation is essential in the initial development and progression of many cardiovascular diseases involving innate and adaptive immune responses. The role of CD4+CD25+FOXP3+ regulatory T (TREG) cells in the modulation of inflammation and immunity has received increasing attention. Given the important role of TREG cells in the induction and maintenance of immune homeostasis and tolerance, dysregulation in the generation or function of TREG cells can trigger abnormal immune responses and lead to pathology. A wealth of evidence from experimental and clinical studies has indicated that TREG cells might have an important role in protecting against cardiovascular disease, in particular atherosclerosis and abdominal aortic aneurysm. In this Review, we provide an overview of the roles of TREG cells in the pathogenesis of a number of cardiovascular diseases, including atherosclerosis, hypertension, ischaemic stroke, abdominal aortic aneurysm, Kawasaki disease, pulmonary arterial hypertension, myocardial infarction and remodelling, postischaemic neovascularization, myocarditis and dilated cardiomyopathy, and heart failure. Although the exact molecular mechanisms underlying the cardioprotective effects of TREG cells are still to be elucidated, targeted therapies with TREG cells might provide a promising and novel future approach to the prevention and treatment of cardiovascular diseases.

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Figure 1: Differentiation of naive T cells into T cell subpopulations.
Figure 2: Mechanisms of TREG cell-mediated suppression and the implicative pathways.
Figure 3: Underlying mechanisms of TREG cells in atherosclerosis.
Figure 4: Underlying mechanisms of TREG cells in AAA.

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Acknowledgements

X.M, J.Y., M.D, K.Z., C.Z. and Y.Z. are supported by the National 973 Basic Research Program of China (2011CB503906, 2012CB518603, 2013CB530703), the National High-Tech Research and Development Program of China (2012AA02A510), the Program of Introducing Talents of Discipline to Universities (B07035), the State Program of National Natural Science Foundation of China for Innovative Research Group (81321061), the State Key Program of National Natural Science of China (61331001), the International Collaboration and Exchange Program of China (81320108004), and research grants from the National Natural Science Foundation of China (81100207, 81173251, 81270350, and 81300234). E.T. and W.C. are supported by the Intramural Research Program of NIH, NIDCR.

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Q.G. researched the data for the article and provided substantial contribution to discussions of the content. M.D., K.Z., and E.T. researched data for the article, provided substantial contribution to discussions of the content, and contributed to writing the article. C.Z., X.M., J.Y., W.C., and Y.Z. researched data for the article, discussed its content, wrote the manuscript, and reviewed/edited it before submission.

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Correspondence to Cheng Zhang.

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Meng, X., Yang, J., Dong, M. et al. Regulatory T cells in cardiovascular diseases. Nat Rev Cardiol 13, 167–179 (2016). https://doi.org/10.1038/nrcardio.2015.169

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