Blocking of programmed cell death-ligand 1 (PD-L1) expressed on endothelial cells promoted the recruitment of CD8+IFN-γ+ T cells in atherosclerosis

作者：Li, Qi; Wei, Simeng; Li, Yue; Wu, Fengjiao; Qin, Xiaoling; Li, Zhongsha; Li, Jingyu; Chen, Chang^*

来源：Inflammation Research, 2023, 72(4): 783-796.

DOI：10.1007/s00011-023-01703-5

• Atherosclerosis
• PD-L1
• Endothelial cell
• CD8(+)IFN-gamma T+ cell
• IFN-gamma

Background Programmed death ligand-1 (PD-L1) is involved in the negative regulation of immune responses in a variety of diseases. We evaluated the contribution of PD-L1 to the activation of immune cells that promote atherosclerotic lesion formation and inflammation.Methods and results Compared to ApoE(-/-) mice that were provided a high-cholesterol diet in combination with anti-PD-L1 antibody developed a larger lipid burden with more abundant CD8(+) T cells. The anti-PD-L1 antibody increased the abundance of CD3(+)PD-1(+), CD8 + PD-1(+),CD3(+)IFN-gamma(+) and CD8(+)IFN-gamma(+) T cell under high-cholesterol diet, as well as the serum tumor necrosis factor-alpha (TNF-a), IFN-gamma, PF, GNLY, Gzms B and LTA. Interestingly, the anti-PD-L1 antibody increased the serum level of sPD-L1. In vitro, blocking of PD-L1 on the surface of mouse aortic endothelial cells with anti-PD-L1 antibody stimulated the activation and secretion of cytokines, including IFN-gamma, PF, GNLY, Gzms B and LTA, from cytolytic CD8(+)IFN-gamma(+) T cell. However, the concentration of sPD-L1 was lower after treatment of the MAECs with anti-PD-L1 antibody.Conclusions Our findings highlighted that blocking of PD-L1 promoted up-regulation of CD8 + IFN-gamma + T cell-mediated immune responses, leading to the secretion of inflammatory cytokine that exacerbated the atherosclerotic burden and promoted inflammation. However, further studies are needed to gain insight into whether PD-L1 activation could be a novel immunotherapy strategy for atherosclerosis.

• 单位
  哈尔滨医科大学