T cell co-stimulator inducible co-stimulatory (ICOS) exerts potential anti-atherosclerotic roles through downregulation of vascular smooth muscle phagocytosis and proliferation

Abstract

Background: Atherosclerosis (AS) is a chronic inflammatory disease. The role of the immune system in the etiology of the disease, particularly T cells, has been widely studied and is well established. T cell activation directly regulates co-signaling molecules present in immune synapses. Targeting one or several of these cosignaling molecules can inhibit T cell-mediated inflammation and delay or reduce AS. In recent years, this strategy has increasingly become a research focus. As such, we explored the role and therapeutic potential of the T cell co-stimulatory molecule inducible co-stimulatory (ICOS) in AS. Methods: We compared the expression of ICOS in early AS lesions occurring in ApoE-deficient (ApoE-KO) rats fed a fat-diet and wild type (WT) rats fed the same diet. Eight-week old ApoE-KO and WT rats [ApoE-KO(0) and WT(0)] were fed a high-fat diet for 16 weeks [ApoE-KO(16) and WT(16)]. ICOS expression in aortic tissues was analyzed by quantitative real-time PCR, western blot, and confocal microscopy. The effect of ICOS overexpression in a transfected human T cell line on the phagocytosis and proliferation of cocultured human aortic smooth muscle cells (HASMCs) was studied in vitro.Results: Compared with WT(0), ApoE-KO(0), and WT(16) rats, ICOS expression in ApoE-KO(16) rats was significantly down-regulated both at the mRNA and protein levels. In vitro experiments indicated that ICOS overexpression reduces phagocytosis and proliferation by HASMCs, and may therefore produce an anti-atherosclerotic effect. Conclusions:The immune synaptic co-signaling molecule ICOS has an anti-atherosclerotic effect through inhibition of HASMC phagocytosis and proliferation, and can be used to delay plaque formation during the early stages of AS.

Inducible co-stimulator inhibits lipid phagocytosis of human aortic smooth muscle cells by down-regulating CD36 expression

“…It has been reported that ICOS may play an antiatherosclerotic role by inhibiting the phagocytosis and proliferation of HASMCs during the formation of atherosclerotic plaques (20). In this experiment, the relationship between ICOS and HASMCs was detected by co-cultivation of JK-ICOS cells and HASMCs.…”

“…However, this was not explicitly verified in the study, and its mechanism was not explored in depth. Our preliminary experiments have found that the expression of ICOS in the aortic atherosclerotic plaques of APOE KO rats was significantly reduced, and the overexpression of ICOS could inhibit the phagocytosis and proliferation of HASMCs (20). This experiment tested the main lipid phagocytic receptors involved and found CD36 has significant differences.…”

“…A stable human T lymphocyte leukemia cell line (JurKat T cell) with ICOS overexpression was constructed using the lentivirus packaging technique (20). HASMCs were derived from the American Type Culture Collection (ATCC) cell bank and cultured in a complete medium of HASMCs (CHI Scientific, China, Cat.…”

“…With the increasing public attention to immune costimulatory molecules, research into ICOS in AS has gradually increased in recent years. Down-regulation of ICOS expression has been detected in aortic atherosclerotic plaques of ApoE −/− rats (20). High-fatfed ICOS gene deficient ApoE −/− mice had a 77% increase in early atherosclerotic plaque, and a 36% increase in late atherosclerotic plaque (19).…”

Costimulatory and coinhibitory molecules of B7-CD28 family in cardiovascular atherosclerosis: A review

“…[ 110 ] In addition, controlling the T follicular helper-germinal center B-cell axis by blocking the CD8 + Treg ICOS-ICOSL pathway could reduce the development of atherosclerosis, [ 111 ] and ICOS has an antiatherosclerotic effect by inhibiting aortic smooth muscle cell phagocytosis and proliferation to delay plaque formation in apoE −/− mouse models. [ 112 ] Furthermore, in a mouse atherosclerosis model, the expression of ICOS in the spleen was decreased, and promoting ICOS activity could provide a useful strategy for the prevention of atherosclerosis.…”