{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T20:28:01Z","timestamp":1791836881929,"version":"4.3.4"},"reference-count":77,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T00:00:00Z","timestamp":1653436800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009379","name":"Interdisziplin\u00e4res Zentrum f\u00fcr Klinische Forschung, Universit\u00e4tsklinikum W\u00fcrzburg","doi-asserted-by":"publisher","award":["E-354"],"award-info":[{"award-number":["E-354"]}],"id":[{"id":"10.13039\/501100009379","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["411619907, 453989101"],"award-info":[{"award-number":["411619907, 453989101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The immune system plays a vital role in maintaining tissue integrity and organismal homeostasis. The sudden stress caused by myocardial infarction (MI) poses a significant challenge for the immune system: it must quickly substitute dead myocardial with fibrotic tissue while controlling overt inflammatory responses. In this review, we will discuss the central role of myocardial regulatory T-cells (Tregs) in orchestrating tissue repair processes and controlling local inflammation in the context of MI. We herein compile recent advances enabled by the use of transgenic mouse models with defined cardiac antigen specificity, explore whole-heart imaging techniques, outline clinical studies and summarize deep-phenotyping conducted by independent labs using single-cell transcriptomics and T-cell repertoire analysis. Furthermore, we point to multiple mechanisms and cell types targeted by Tregs in the infarcted heart, ranging from pro-fibrotic responses in mesenchymal cells to local immune modulation in myeloid and lymphoid lineages. We also discuss how both cardiac-specific and polyclonal Tregs participate in MI repair. In addition, we consider intriguing novel evidence on how the myocardial milieu takes control of potentially auto-aggressive local immune reactions by shaping myosin-specific T-cell development towards a regulatory phenotype. Finally, we examine the potential use of Treg manipulating drugs in the clinic after MI.<\/jats:p>","DOI":"10.3389\/fimmu.2022.914033","type":"journal-article","created":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T06:56:07Z","timestamp":1653461767000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["Myocardial-Treg Crosstalk: How to Tame a Wolf"],"prefix":"10.3389","volume":"13","author":[{"given":"Emil","family":"Wei\u00df","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo Campos","family":"Ramos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murilo","family":"Delgobo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-018-0065-8","article-title":"Cardioimmunology: The Immune System in Cardiac Homeostasis and Disease","volume":"18","author":"Swirski","year":"2018","journal-title":"Nat Rev Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.03.050","article-title":"Macrophages Facilitate Electrical Conduction in the Heart","volume":"169","author":"Hulsmans","year":"2017","journal-title":"Cell"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehv639","article-title":"Role of T-cells in Myocardial Infarction","volume":"37","author":"Hofmann","year":"2016","journal-title":"Eur Heart J"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.115.002225","article-title":"Left Ventricular T-Cell Recruitment Contributes to the Pathogenesis of Heart Failure","volume":"8","author":"Nevers","year":"2015","journal-title":"Circ Heart Fail"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14680","article-title":"T Cell Costimulation Blockade Blunts Pressure Overload-Induced Heart Failure","volume":"8","author":"Kallikourdis","year":"2017","journal-title":"Nat Commun"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1502139","article-title":"Cutting Edge: Regulatory T Cells Facilitate Cutaneous Wound Healing","volume":"196","author":"Nosbaum","year":"2016","journal-title":"J Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-042718-041717","article-title":"Regulatory T Cells and Human Disease","volume":"38","author":"Sakaguchi","year":"2020","journal-title":"Annu Rev Immunol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.08.021","article-title":"A Distinct Function of Regulatory T Cells in Tissue Protection","volume":"162","author":"Arpaia","year":"2015","journal-title":"Cell"},{"key":"B9","doi-asserted-by":"crossref","DOI":"10.4049\/jimmunol.155.3.1151","article-title":"Immunologic Self-Tolerance Maintained by Activated T Cells Expressing IL-2 Receptor Alpha-Chains (CD25). Breakdown of a Single Mechanism of Self-Tolerance Causes Various Autoimmune Diseases","volume":"155","author":"Sakaguchi","year":"1995","journal-title":"J Immunol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/83713","article-title":"The Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-linked Syndrome (IPEX) Is Caused by Mutations of FOXP3","volume":"27","author":"Bennett","year":"2001","journal-title":"Nat Genet"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1126\/science.1079490","article-title":"Control of Regulatory T Cell Development by the Transcription Factor Foxp3","volume":"299","author":"Hori","year":"2003","journal-title":"Science"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/ni904","article-title":"Foxp3 Programs the Development and Function of CD4+CD25+ Regulatory T Cells","volume":"4","author":"Fontenot","year":"2003","journal-title":"Nat Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1242\/dev.104.4.619","article-title":"Implants of Quail Thymic Epithelium Generate Permanent Tolerance in Embryonically Constructed Quail\/Chick Chimeras","volume":"104","author":"Ohki","year":"1988","journal-title":"Development"},{"key":"B14","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/0092-8674(94)90419-7","article-title":"High Incidence of Spontaneous Autoimmune Encephalomyelitis in Immunodeficient Anti-Myelin Basic Protein T Cell Receptor Transgenic Mice","volume":"78","author":"Lafaille","year":"1994","journal-title":"Cell"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/ni1037","article-title":"Regulatory T Cells Mediate Maternal Tolerance to the Fetus","volume":"5","author":"Aluvihare","year":"2004","journal-title":"Nat Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032712-095948","article-title":"Tissue Tregs","volume":"34","author":"Panduro","year":"2016","journal-title":"Annu Rev Immunol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/nature11132","article-title":"PPAR-Gamma Is a Major Driver of the Accumulation and Phenotype of Adipose Tissue Treg Cells","volume":"486","author":"Cipolletta","year":"2012","journal-title":"Nature"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.10.054","article-title":"A Special Population of Regulatory T Cells Potentiates Muscle Repair","volume":"155","author":"Burzyn","year":"2013","journal-title":"Cell"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.01.009","article-title":"Poor Repair of Skeletal Muscle in Aging Mice Reflects a Defect in Local, Interleukin-33-Dependent Accumulation of Regulatory T Cells","volume":"44","author":"Kuswanto","year":"2016","journal-title":"Immunity"},{"key":"B20","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1016\/j.immuni.2019.01.001","article-title":"Single-Cell Transcriptomics of Regulatory T Cells Reveals Trajectories of Tissue Adaptation","volume":"50","author":"Miragaia","year":"2019","journal-title":"Immunity"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000617","article-title":"Cardiac Myosin Induces Myocarditis in Genetically Predisposed Mice","volume":"139","author":"Neu","year":"1987","journal-title":"J Immunol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/nm960","article-title":"Dendritic Cell-Induced Autoimmune Heart Failure Requires Cooperation Between Adaptive and Innate Immunity","volume":"9","author":"Eriksson","year":"2003","journal-title":"Nat Med"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2016.01.018","article-title":"Myocardial Fibrosis Seen Through the Lenses of T-cell Biology","volume":"92","author":"Ramos","year":"2016","journal-title":"J Mol Cell Cardiol"},{"key":"B24","doi-asserted-by":"crossref","DOI":"10.1161\/CIR.0000000000000617","article-title":"Fourth Universal Definition of Myocardial Infarction (2018)","volume":"138","author":"Thygesen","year":"2018","journal-title":"Circulation"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.044164","article-title":"Activation of CD4+ T Lymphocytes Improves Wound Healing and Survival After Experimental Myocardial Infarction in Mice","volume":"125","author":"Hofmann","year":"2012","journal-title":"Circulation"},{"key":"B26","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1007\/s00395-011-0232-6","article-title":"Regulatory T Cells Ameliorate Cardiac Remodeling After Myocardial Infarction","volume":"107","author":"Tang","year":"2012","journal-title":"Basic Res Cardiol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1161\/CIRCRESAHA.115.303895","article-title":"Foxp3+ Cd4+ T Cells Improve Healing After Myocardial Infarction by Modulating Monocyte\/Macrophage Differentiation","volume":"115","author":"Weirather","year":"2014","journal-title":"Circ Res"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.107.144824","article-title":"Osteopontin: A Multifunctional Molecule Regulating Chronic Inflammation and Vascular Disease","volume":"27","author":"Scatena","year":"2007","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1007\/s00395-017-0622-5","article-title":"Il-10 Improves Cardiac Remodeling After Myocardial Infarction by Stimulating M2 Macrophage Polarization and Fibroblast Activation","volume":"112","author":"Jung","year":"2017","journal-title":"Basic Res Cardiol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2004.07.017","article-title":"Inhibition of TGF-beta Signaling Exacerbates Early Cardiac Dysfunction But Prevents Late Remodeling After Infarction","volume":"64","author":"Ikeuchi","year":"2004","journal-title":"Cardiovasc Res"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00328.2014","article-title":"Regulatory T Cells Are Recruited in the Infarcted Mouse Myocardium and may Modulate Fibroblast Phenotype and Function","volume":"307","author":"Saxena","year":"2014","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1042\/CS20140672","article-title":"Activated Regulatory T-cells Attenuate Myocardial Ischaemia\/Reperfusion Injury Through a CD39-dependent Mechanism","volume":"128","author":"Xia","year":"2015","journal-title":"Clin Sci (Lond)"},{"key":"B33","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1161\/CIRCULATIONAHA.116.023365","article-title":"CD73 on T Cells Orchestrates Cardiac Wound Healing After Myocardial Infarction by Purinergic Metabolic Reprogramming","volume":"136","author":"Borg","year":"2017","journal-title":"Circulation"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.036053","article-title":"C-X-C Motif Chemokine Receptor 4 Blockade Promotes Tissue Repair After Myocardial Infarction by Enhancing Regulatory T Cell Mobilization and Immune-Regulatory Function","volume":"139","author":"Wang","year":"2019","journal-title":"Circulation"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.121.055888","article-title":"Ccl17 Aggravates Myocardial Injury by Suppressing Recruitment of Regulatory T-Cells","volume":"14","author":"Feng","year":"2022","journal-title":"Circulation"},{"key":"B36","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1172\/JCI88759","article-title":"Epicardial YAP\/TAZ Orchestrate an Immunosuppressive Response Following Myocardial Infarction","volume":"127","author":"Ramjee","year":"2017","journal-title":"J Clin Invest"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1172\/JCI123859","article-title":"Myocardial Infarction Triggers Cardioprotective Antigen-Specific T Helper Cell Responses","volume":"129","author":"Rieckmann","year":"2019","journal-title":"J Clin Invest"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201142209","article-title":"Cooperation of Th1 and Th17 Cells Determines Transition From Autoimmune Myocarditis to Dilated Cardiomyopathy","volume":"42","author":"Nindl","year":"2012","journal-title":"Eur J Immunol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1126\/science.aav3487","article-title":"Microbiota-Derived Peptide Mimics Drive Lethal Inflammatory Cardiomyopathy","volume":"366","author":"Gil-Cruz","year":"2019","journal-title":"Science"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1101\/2022.03.25.485791","article-title":"Rapid Differentiation of Regulatory CD4+ T Cells in the Infarcted Myocardium Blunts in Situ Inflammation","volume":"2022","author":"Delgobo","year":"2022","journal-title":"bioRxiv"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.19.9131","article-title":"Expression of Myosin-Class II Major Histocompatibility Complexes in the Normal Myocardium Occurs Before Induction of Autoimmune Myocarditis","volume":"89","author":"Smith","year":"1992","journal-title":"Proc Natl Acad Sci USA"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1172\/JCI44583","article-title":"Impaired Thymic Tolerance to Alpha-Myosin Directs Autoimmunity to the Heart in Mice and Humans","volume":"121","author":"Lv","year":"2011","journal-title":"J Clin Invest"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.02.079","article-title":"Myocardial Infarction Primes Autoreactive T Cells Through Activation of Dendritic Cells","volume":"18","author":"Van der Borght","year":"2017","journal-title":"Cell Rep"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.046789","article-title":"A Unique Population of\u00a0Regulatory T Cells in Heart Potentiates Cardiac Protection From Myocardial Infarction","volume":"142","author":"Xia","year":"2020","journal-title":"Circulation"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2015.169","article-title":"Regulatory T Cells in Cardiovascular Diseases","volume":"13","author":"Meng","year":"2016","journal-title":"Nat Rev Cardiol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02795","article-title":"Getting to the Heart of the Matter: The Role of Regulatory T-Cells (Tregs) in Cardiovascular Disease (CVD) and Atherosclerosis","volume":"10","author":"Albany","year":"2019","journal-title":"Front Immunol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.036065","article-title":"Dysfunctional and Proinflammatory Regulatory T-Lymphocytes Are Essential for Adverse Cardiac Remodeling in Ischemic Cardiomyopathy","volume":"139","author":"Bansal","year":"2019","journal-title":"Circulation"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.041694","article-title":"Single-Cell Sequencing of Mouse Heart Immune Infiltrate in Pressure Overload-Driven Heart Failure Reveals Extent of Immune Activation","volume":"140","author":"Martini","year":"2019","journal-title":"Circulation"},{"key":"B49","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.imlet.2020.04.006","article-title":"Differences in T Regulatory Cells Between Mouse Strains Frequently Used in Immunological Research: Treg Cell Quantities and Subpopulations in NOD, B6 and BALB\/c Mice","volume":"223","author":"Godoy","year":"2020","journal-title":"Immunol Lett"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0604341","article-title":"BALB\/C Mice Have More CD4+CD25+ T Regulatory Cells and Show Greater Susceptibility to Suppression of Their CD4+CD25- Responder T Cells Than C57BL\/6 Mice","volume":"78","author":"Chen","year":"2005","journal-title":"J Leukoc Biol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20021893","article-title":"Cd4+ T Cell Polarization in Mice Is Modulated by Strain-Specific Major Histocompatibility Complex-Independent Differences Within Dendritic Cells","volume":"198","author":"Filippi","year":"2003","journal-title":"J Exp Med"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2015.07.008","article-title":"Reversal of Mitochondrial Transhydrogenase Causes Oxidative Stress in Heart Failure","volume":"22","author":"Nickel","year":"2015","journal-title":"Cell Metab"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvab157","article-title":"Coping With Sterile Inflammation: Between Risk and Necessity","volume":"117","author":"Ashour","year":"2021","journal-title":"Cardiovasc Res"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0352-z","article-title":"Functional Categories of Immune Inhibitory Receptors","volume":"20","author":"Rumpret","year":"2020","journal-title":"Nat Rev Immunol"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20090847","article-title":"Pd-L1 Regulates the Development, Maintenance, and Function of Induced Regulatory T Cells","volume":"206","author":"Francisco","year":"2009","journal-title":"J Exp Med"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.142909","article-title":"Overexpression of PD-1 on T Cells Promotes Tolerance in Cardiac Transplantation Via ICOS-dependent Mechanisms","volume":"6","author":"Borges","year":"2021","journal-title":"JCI Insight"},{"key":"B57","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1016\/j.immuni.2022.02.006","article-title":"Single-Cell Immunology: Past, Present, and Future","volume":"55","author":"Ginhoux","year":"2022","journal-title":"Immunity"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1126\/science.1200708","article-title":"Transient Regenerative Potential of the Neonatal Mouse Heart","volume":"331","author":"Porrello","year":"2011","journal-title":"Science"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.18632\/aging.100526","article-title":"Complete Cardiac Regeneration in a Mouse Model of Myocardial Infarction","volume":"4","author":"Haubner","year":"2012","journal-title":"Aging (Albany NY)"},{"key":"B60","doi-asserted-by":"publisher","first-page":"2432","DOI":"10.1038\/s41467-018-04908-z","article-title":"Paracrine Effect of Regulatory T Cells Promotes Cardiomyocyte Proliferation During Pregnancy and After Myocardial Infarction","volume":"9","author":"Zacchigna","year":"2018","journal-title":"Nat Commun"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.7150\/thno.32734","article-title":"Regulatory T-cells Regulate Neonatal Heart Regeneration by Potentiating Cardiomyocyte Proliferation in a Paracrine Manner","volume":"9","author":"Li","year":"2019","journal-title":"Theranostics"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2017.11.010","article-title":"Zebrafish Regulatory T Cells Mediate Organ-Specific Regenerative Programs","volume":"43","author":"Hui","year":"2017","journal-title":"Dev Cell"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehac153","article-title":"Adult T-cells Impair Neonatal Cardiac Regeneration","volume":"43","author":"Dolejsi","year":"2022","journal-title":"Eur Heart J"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1914848116","article-title":"T Cell Receptor Specificity Drives Accumulation of a Reparative Population of Regulatory T Cells Within Acutely Injured Skeletal Muscle","volume":"116","author":"Cho","year":"2019","journal-title":"Proc Natl Acad Sci USA"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1922559117","article-title":"Neuronal, Stromal, and T-regulatory Cell Crosstalk in Murine Skeletal Muscle","volume":"117","author":"Wang","year":"2020","journal-title":"Proc Natl Acad Sci USA"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1707914","article-title":"Antiinflammatory Therapy With Canakinumab for Atherosclerotic Disease","volume":"377","author":"Ridker","year":"2017","journal-title":"N Engl J Med"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.00695","article-title":"Mediastinal Lymphadenopathy, Class-Switched Auto-Antibodies and Myocardial Immune-Complexes During Heart Failure in Rodents and Humans","volume":"8","author":"Sintou","year":"2020","journal-title":"Front Cell Dev Biol"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/6079713","article-title":"The Prognostic Impact of Circulating Regulatory T Lymphocytes on Mortality in Patients With Ischemic Heart Failure With Reduced Ejection Fraction","volume":"2020","author":"Hammer","year":"2020","journal-title":"Mediators Inflammation"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.112.251579","article-title":"Low Levels of Circulating CD4+Foxp3+ T Cells Are Associated With an Increased Risk for Development of Myocardial Infarction But Not for Stroke","volume":"32","author":"Wigren","year":"2012","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehl222","article-title":"Altered Status of CD4(+)CD25(+) Regulatory T Cells in Patients With Acute Coronary Syndromes","volume":"27","author":"Mor","year":"2006","journal-title":"Eur Heart J"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2016.07.035","article-title":"The Ratio of Regulatory (FOXP3+) to Total (Cd3+) T Cells Determined by Epigenetic Cell Counting and Cardiovascular Disease Risk: A Prospective Case-cohort Study in Non-Diabetics","volume":"11","author":"Barth","year":"2016","journal-title":"EBioMedicine"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1536\/ihj.13-343","article-title":"Prognostic Value of Circulating Regulatory T Cells for Worsening Heart Failure in Heart Failure Patients With Reduced Ejection Fraction","volume":"55","author":"Okamoto","year":"2014","journal-title":"Int Heart J"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2012.00268","article-title":"Competition for IL-2 Between Regulatory and Effector T Cells to Chisel Immune Responses","volume":"3","author":"Hofer","year":"2012","journal-title":"Front Immunol"},{"key":"B74","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1038\/s41392-017-0002-5","article-title":"Targeting IL-2: An Unexpected Effect in Treating Immunological Diseases","volume":"3","author":"Ye","year":"2018","journal-title":"Signal Transd Target Ther"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2018-022452","article-title":"Low-Dose Interleukin-2 in Patients With Stable Ischaemic Heart Disease and Acute Coronary Syndromes (LILACS): Protocol and Study Rationale for a Randomised, Double-Blind, Placebo-Controlled, Phase I\/II Clinical Trial","volume":"8","author":"Zhao","year":"2018","journal-title":"BMJ Open"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1056\/EVIDoa2100009","article-title":"Regulatory T-Cell Response to Low-Dose Interleukin-2 in Ischemic Heart Disease","volume":"1","author":"Zhao","year":"2022","journal-title":"NEJM Evid"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1126\/science.abm0594","article-title":"Car T Cells Produced In Vivo to Treat Cardiac Injury","volume":"375","author":"Rurik","year":"2022","journal-title":"Science"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.914033\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T04:26:12Z","timestamp":1675657572000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.914033\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,25]]},"references-count":77,"alternative-id":["10.3389\/fimmu.2022.914033"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.914033","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,25]]},"article-number":"914033"}}