Regulatory T cells in atherosclerosis: critical immune regulatory function and therapeutic potential

• Published in: Cellular and molecular life sciences : CMLS 2016-03, Vol.73 (5), p.901-922
• Main Authors: Spitz, Charlotte, Winkels, Holger, Bürger, Christina, Weber, Christian, Lutgens, Esther, Hansson, Göran K, Gerdes, Norbert
• Format: Article
• Language: English
• Subjects: adaptive immunity; Adoptive Transfer; Animals; atherogenesis; Atherosclerosis; Atherosclerosis - immunology; Atherosclerosis - pathology; Atherosclerosis - prevention & control; Atherosclerosis - therapy; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cardiovascular diseases; Cell Biology; cell proliferation; Cellular biology; complications (disease); Cytokines; Humans; immune response; Immune system; Immunity, Cellular; Immunization - methods; interleukin-10; Life Sciences; Lipids; Lymphocytes; mice; Myocardial infarction; Review; secretion; stroke; T-lymphocytes; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - pathology
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s00018-015-2080-2

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.