Disruption of the CCL1-CCR8 axis inhibits vascular Treg recruitment and function and promotes atherosclerosis in mice. (July 2019)

• Record Type: Journal Article
• Authors: Vila-Caballer, Marian; González-Granado, José M.; Zorita, Virginia; Abu Nabah, Yafa N.; Silvestre-Roig, Carlos; del Monte-Monge, Alberto; Molina-Sánchez, Pedro; Ait-Oufella, Hafid; Andrés-Manzano, María J.; Sanz, María J.; Weber, Christian; Kremer, Leonor; Gutiérrez, Julio; Mallat, Ziad; Andrés, Vicente
• Is Part Of: Journal of molecular and cellular cardiology. Volume 132(2019)
• Page Start: 154
• Page End: 163
• Publication Date: 2019-07
• Subjects: Atherosclerosis -- CCL1 -- CCR8 -- Treg -- IL-10; Apoe apolipoprotein E -- Apoe-KO apolipoprotein E-null mice -- Apoe/Ccl1-DKO apolipoprotein E-CCL1 doubly-deficient mice -- BMdM bone marrow-derived macrophage -- CCL1 CC chemokine 1 (also named TCA3 and I-309) -- CCR8 C-C motif chemokine receptor 8 -- HFD high-fat diet -- IL-10 interleukin 10 -- Ldlr-KO low-density lipoprotein receptor-null mice -- RFP red fluorescent protein -- Th helper T cell -- Treg regulatory T cell -- VSMC vascular smooth muscle cell; Cardiology -- Periodicals; Heart Diseases -- Periodicals; Molecular Biology -- Periodicals; Cardiologie -- Périodiques; Cardiology; Electronic journals; Periodicals; 616.12
• DOI: 10.1016/j.yjmcc.2019.05.009
• Languages: English
• ISSNs: 0022-2828

Abstract

Abstract: The CC chemokine 1 (CCL1, also called I-309 or TCA3) is a potent chemoattractant for leukocytes that plays an important role in inflammatory processes and diseases through binding to its receptor CCR8. Here, we investigated the role of the CCL1-CCR8 axis in atherosclerosis. We found increased expression of CCL1 in the aortas of atherosclerosis-prone fat-fed apolipoprotein E ( Apoe )-null mice; moreover, in vitro flow chamber assays and in vivo intravital microscopy demonstrated an essential role for CCL1 in leukocyte recruitment. Mice doubly deficient for CCL1 and Apoe exhibited enhanced atherosclerosis in aorta, which was associated with reduced plasma levels of the anti-inflammatory interleukin 10, an increased splenocyte Th1/Th2 ratio, and a reduced regulatory T cell (Treg) content in aorta and spleen. Reduced Treg recruitment and aggravated atherosclerosis were also detected in the aortas of fat-fed low-density lipoprotein receptor-null mice treated with CCR8 blocking antibodies. These findings demonstrate that disruption of the CCL1-CCR8 axis promotes atherosclerosis by inhibiting interleukin 10 production and Treg recruitment and function. Highlights: CCL1 ablation impairs vascular Treg recruitment and function. CCL1 ablation is associated with reduced IL-10 production, impaired Th2 response, and increased Th1 response. Inactivation of CCL1-CCR8 axis aggravates atherosclerosis development.