Impact of immune checkpoint TIGIT on the activation and function of natural killer cells in rheumatoid arthritis patients

Abstract

Objectives This study aims to investigate the changes of circulating natural killer (NK) cells and their TIGIT expression diversities, and further explore the impact of TIGIT expression on the activity and function of NK cells in rheumatoid arthritis (RA) patients. Methods We comparatively assessed and compared the changes of NK cells, as well as their TIGIT expressions, among fifty-three cases of RA patients, twenty-three cases of healthy controls (HCs) and eleven osteoarthritis (OA) patients using flow cytometry and in-vitro cultures. CD25 and CD69 expression levels were used to evaluate the activation of NK subsets, and CD107α and GZMB expressions levels, IFN-γ production abilities were detected to indicate the functions of NK subsets. Results Circulating CD56brightNK cell levels were significantly elevated, while NKT cell levels were notably reduced in RA patients. In addition, NK cells manifested more activated phenotypes and enhanced functions in RA. Meanwhile, TIGIT expression on NK cells and subsets was significantly reduced, with an imbalanced TIGIT/CD226 ratio. TIGIT-expressing NK subsets showed lower CD25 expression levels and weakened IFN-γ production abilities in RA patients. Furthermore, in-vitro blockade of TIGIT-pathway with anti-TIGIT antibody enhanced NK cell activity and functions while activation of TIGIT-pathway with TIGIT-Fc chimera protein down-regulated NK cells activity and function. Conclusion Our results showed that decreased TIGIT expressions in RA patients and the TIGIT signalling pathway may participate in the activation and function of NK subsets, which show new insight for the exploration of RA pathogenesis.