Imbalance of the CD226/TIGIT Immune Checkpoint Is Involved in the Pathogenesis of Primary Biliary Cholangitis

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, γ-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, γ-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-γ ⁺, and TNF-α ⁺ 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 subset in vitro.