Downregulation of Programmed Death-1 Pathway Promoting CD8 + T Cell Cytotoxicity in Primary Biliary Cholangitis.
Dig Dis Sci
; 67(7): 2981-2993, 2022 07.
Article
em En
| MEDLINE
| ID: mdl-34392493
ABSTRACT
BACKGROUND:
Primary biliary cholangitis (PBC) is an autoimmune disease. CD8 + T cell (CTLs) cytotoxicity played a crucial rule in of PBC with unclear detailed pathogenesis.AIMS:
The role of the programmed death-1 (PD-1) pathway in CD8 + T cell cytotoxicity in patients with PBC was determined.METHODS:
We recruited 69 patients with PBC and 57 healthy controls (HCs). PD-1 pathway in peripheral CD8 + T cells and related cytokines were detected, and gene expression levels were detected. Immunofluorescence staining of PD-1/PD-L1 was performed on liver tissue. PD-1 ± CTLs were cocultured with human intrahepatic biliary epithelial cells (HiBECs) to measure CTL cytotoxicity, proliferation and cytokine levels and HiBEC apoptosis. The upstream signaling pathway of PD-1 was detected.RESULTS:
PBC patients exhibited Tbet gene upregulation and PD-1 downregulation in CTLs, with PD-1 expression reduced in CTLs and PD-L1 reduced in the liver portal region relative to HCs. Higher plasma IL-10, interferon-γ and transforming growth factor-ß concentrations were observed in the PBC group than the HC group. In CTL and HiBEC coculture experiment, compared with PD-1- CTLs, PD-1 + CTLs exhibited weaker cytotoxicity, less proliferation and lower cytokine production. When the system was blocked by anti-PD-1 antibodies, these effects were antagonized.CONCLUSIONS:
PD-1 expression in CD8 + T cells decreased, and PD-1 pathway-related cytokines changed in patients with PBC. PD-1/PD-L1 pathway silencing increased CD8 + T cell proliferation, related cytokine production and CTL cytotoxic effects on HiBECs in coculture experiment. The PD-1/PD-L1 pathway might represent an important pathway in the immunological mechanism underlying PBC.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Antígeno B7-H1
/
Cirrose Hepática Biliar
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article