T cells in cardiac health and disease
Pilar Martín, Francisco Sánchez-Madrid
Pilar Martín, Francisco Sánchez-Madrid
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Review

T cells in cardiac health and disease

Abstract

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide, with inflammation playing a pivotal role in its pathogenesis. T lymphocytes are crucial components of the adaptive immune system that have emerged as key mediators in both cardiac health and the development and progression of CVD. This Review explores the diverse roles of T cell subsets, including Th1, Th17, γδ T cells, and Tregs, in myocardial inflammatory processes such as autoimmune myocarditis and myocardial infarction. We discuss the contribution of T cells to myocardial injury and remodeling, with emphasis on specific immune receptors, e.g., CD69, that have a critical role in regulating immune tolerance and maintaining the balance between T cell subsets in the heart. Additionally, we offer a perspective on recent advances in T cell–targeted therapies and their potential to modulate immune responses and improve clinical outcomes in patients with CVD and in heart transplant recipients. Understanding the intricate interplay between T cells and cardiovascular pathology is essential for developing novel immunotherapeutic strategies against CVD.

Authors

Pilar Martín, Francisco Sánchez-Madrid

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Figure 1

The role of CD69 in various cardiovascular pathologies.

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The role of CD69 in various cardiovascular pathologies. (A) oxLDL bindin...
(A) oxLDL binding to the CD69 receptor regulates NR4A expression in T cells, which has been shown to promote Treg differentiation. In mice, CD69 deficiency has been linked to altered NR4A1 expression, Treg–Th17 cell imbalance, and exacerbation of atherosclerosis. oxLDL/CD69 signaling also regulates PD-1 expression in CD4+ T cells, which is known to regulate vascular changes in the inflamed aorta. (B) The CD69 receptor’s interaction with oxLDL, Gal-1, and S100A8/S100A9 regulates the FOXP3/RORγt pathway to promote Treg differentiation. In models of myocarditis and dilated cardiomyopathy, CD69–/– hearts have altered Treg–Th17 cell immune cell infiltration and altered RORγt/Foxp3 signaling. (C) In models of myocardial ischemia, CD69 deficiency increases infarct size. CD69 is linked to activation of the aryl hydrocarbon receptor (AhR) and increased CD39 transcription, which promotes Treg control of γδ T cell activity.