Journal
FRONTIERS IN IMMUNOLOGY
Volume 11, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2020.01619
Keywords
primary biliary cholangitis; CD226; TIGIT; immune checkpoint; pathogenesis
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Funding
- National Natural Science Foundation of China [81671618, 81871302]
- CAMS Initiative for Innovative Medicine [2017-I2M-3-001, 2017-I2M-BR-01]
- Youth Research Fund of Peking Union Medical College Hospital [pumch201911238]
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The relationship between the cluster of differentiation 226 (CD226)/T cell Ig and ITIM domain (TIGIT) immune checkpoint and primary biliary cholangitis (PBC) pathogenesis is unknown. Herein, PBC patients (n = 42) showed significantly higher proportions of peripheral CD8(+)T and CD4(+)T cells expressing either CD226 or TIGIT than disease (n = 25) and healthy (n = 30) controls. The percentage of CD8(+) TIGIT(+) T cell was negatively associated with total bilirubin, direct bilirubin, total bile acid, gamma-glutamyl transpeptidase, and alkaline phosphatase, but positively correlated with platelet count; alkaline phosphatase was positively associated with the frequency of CD8(+)CD226(+) T cell; and the CD226/TIGIT ratio of CD8(+) T cell was positively associated with total bilirubin, direct bilirubin, total bile acid, gamma-glutamyl transpeptidase, alkaline phosphatase, and aspartate aminotransferase to platelet ratio, but negatively correlated with albumin and platelet count. The effector function of CD8(+)CD226(+) T cells was more robust than the CD8(+)CD226(-)counterparts. CD226 blockade reduced CD107a(+), IFN-gamma(+), and TNF-alpha(+) proportions among CD8(+)CD226(+) T cells, inhibiting CD8(+) T cell proliferation. In conclusion, CD226/TIGIT immune checkpoint imbalance is involved in the pathogenesis of PBC. The CD226/TIGIT ratio of CD8(+) T cell is a potential biomarker for evaluating the disease status and the prognosis of PBC patients. Moreover, CD8(+)CD226(+) T cells represent a possible therapeutic target for PBC, and blocking CD226 could inhibit the activity of this cell subsetin vitro.
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