title: Regulatory T cells in atherosclerosis: critical immune regulatory function and therapeutic potential.
abstract: Atherosclerosis is a chronic inflammatory disease that is mediated by innate and adaptive immune responses. The disease is characterized by sub-endothelial accumulation and modification of lipids in the artery wall triggering an inflammatory reaction which promotes lesion progression and eventual plaque rupture, thrombus formation, and the respective clinical sequelae such as myocardial infarction or stroke. During the past decade, T-cell-mediated immune responses, especially control of pro-inflammatory signals by regulatory T cells (Tregs), have increasingly attracted the interest of experimental and clinical researchers. By suppression of T cell proliferation and secretion of anti-inflammatory cytokines, such as interleukin-10 (IL-10) and transforming growth factor-β, Tregs exert their atheroprotective properties. Atherosclerosis-prone, hyperlipidemic mice harbor systemically less Tregs compared to wild-type mice, suggesting an imbalance of immune cells which affects local and systemic inflammatory and potentially metabolic processes leading to atherogenesis. Restoring or increasing Treg frequency and enhancing their suppressive capacity by various modulations may pose a promising approach for treating inflammatory conditions such as cardiovascular diseases. In this review, we briefly summarize the immunological basics of atherosclerosis and introduce the role and contribution of different subsets of T cells. We then discuss experimental data and current knowledge pertaining to Tregs in atherosclerosis and perspectives on manipulating the adaptive immune system to alleviate atherosclerosis and cardiovascular disease.
authors.affiliation: Institute for Cardiovascular Prevention, Ludwig-Maximilians University Munich, Pettenkoferstr. 9, 80336, Munich, Germany.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Spitz
authors.affiliation: Institute for Cardiovascular Prevention, Ludwig-Maximilians University Munich, Pettenkoferstr. 9, 80336, Munich, Germany.|Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Holger
authors.initials: H
authors.lastname: Winkels
authors.affiliation: Institute for Cardiovascular Prevention, Ludwig-Maximilians University Munich, Pettenkoferstr. 9, 80336, Munich, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Bürger
authors.affiliation: Institute for Cardiovascular Prevention, Ludwig-Maximilians University Munich, Pettenkoferstr. 9, 80336, Munich, Germany.|DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Weber
authors.affiliation: Institute for Cardiovascular Prevention, Ludwig-Maximilians University Munich, Pettenkoferstr. 9, 80336, Munich, Germany.|Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Esther
authors.initials: E
authors.lastname: Lutgens
authors.affiliation: Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
authors.forename: Göran K
authors.initials: GK
authors.lastname: Hansson
authors.affiliation: Institute for Cardiovascular Prevention, Ludwig-Maximilians University Munich, Pettenkoferstr. 9, 80336, Munich, Germany. norbert.gerdes@med.uni-muenchen.de.
authors.forename: Norbert
authors.identifier: http://orcid.org/0000-0002-4546-7208
authors.initials: N
authors.lastname: Gerdes
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D050197:Atherosclerosis / Q000276:immunology* / Q000473:pathology* / Q000517:prevention & control / Q000628:therapy; D006801:Humans; D007111:Immunity, Cellular; D007114:Immunization / Q000379:methods; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology*
keywords: Antigen; Apoe; CD4+ T cells; Hyperlipidemia; Immunization; LDL; Therapeutic options; Tolerance