AUTHOR=Deng Chuiwen , Li Wenli , Fei Yunyun , Wang Li , Chen Yingying , Zeng Xiaofeng , Zhang Fengchun , Li Yongzhe TITLE=Imbalance of the CD226/TIGIT Immune Checkpoint Is Involved in the Pathogenesis of Primary Biliary Cholangitis JOURNAL=Frontiers in Immunology VOLUME=11 YEAR=2020 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.01619 DOI=10.3389/fimmu.2020.01619 ISSN=1664-3224 ABSTRACT=

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.