PD-L1 inhibits and regulates liver CD8+IFN-γ+ T cells to damage liver function and participate in atherosclerosis
10.12360/CPB202409093
- VernacularTitle:PD-L1抑制促肝源性CD8+IFN-γ+ T细胞损伤肝脏功能参与动脉粥样硬化
- Author:
Xiao LIU
1
;
Xin WU
;
Zi-yi ZHEN
;
Jia-ying ZHANG
;
Qi LI
;
Chang CHEN
Author Information
1. 哈尔滨医科大学药学院药理学教研室
- Publication Type:Journal Article
- Keywords:
atherosclerosis;
PD-L1;
CD8+IFN-γ+T cells;
immune activation;
inflammatory factors;
in-flammatory response
- From:
Chinese Pharmacological Bulletin
2025;41(4):638-645
- CountryChina
- Language:Chinese
-
Abstract:
Aim To study the effect of anti-PD-L1 monoclonal antibody on high-fat diet-induced athero-sclerosis in ApoE-/-mice.Methods Twenty-four ApoE-/-mice were randomly divided into the normal group,high-fat group,and high-fat+anti-PD-L1 mAb group.After 70 days,the blood samples were harves-ted.Blood vessels(aortic root to abdominal aorta)and liver from each groups were stained with Oil Red O.Hematoxylin-eosin staining(HE)was employed to vis-ualize structural changes in liver.Enzyme-linked im-munosorbent assay(ELISA)was applied to detect the serum levels of total cholesterol(CHO),triglyceride(TG),high-density lipoprotein(HDL-c),low-density lipoprotein(LDL-c)and inflammatory factors(IFN-γ,TNF-α,IL-1 β).Flow cytometry was used to detect the proportion of lymphocytes(CD4 and CD8).RT-PCR was utilized to assess the expressions of IFN-γ,TNF-α,IL-1 β,CD4 and CD8 in liver.Results Compared with the high-fat group,the treatment with anti-PD-L1 monoclonal antibody promoted vascular wall and liver lipid accumulation,and also up-regulated serum and liver content of cholesterol(CHO),triglyceride(TG)and high-density lipoprotein(HDL-c).Treatment with anti-PD-L1 monoclonal antibody up-regulated the con-tent of alanine aminotransferase(GPT)and aspartate aminotransferase(GOT)in serum and liver,but not al-kaline phosphatase(AKP).ELISA test indicated that treatment with anti-PD-L1 monoclonal antibody stimu-lated the serum level of IFN-γ,TNF-α and IL-1 β.Fur-thermore,the mRNA level of IFN-γ,TNF-α and IL-1 βin liver was also up-regulated after treatment with anti-PD-L1 monoclonal antibody.With flow cytometry,we observed that treatment with anti-PD-L1 monoclonal antibody promoted hepatic CD8+T and CD8+IFN-γ+T cell activation,but had no effect on CD4+IFN-γ+T cell activation under high-fat feeding conditions.Con-clusions Anti-PD-L1 monoclonal antibody adminis-tered under high-fat feeding conditions can damage liv-er function and aggravate atherosclerosis by activating liver CD8+IFN-γ+T cells.
