TIGIT overexpression diminishes the function of CD4 T cells and ameliorates the severity of rheumatoid arthritis in mouse models

• Published in: Experimental cell research Vol. 340; no. 1; pp. 132 - 138
• Main Authors: Zhao, Weigong, Dong, Yanying, Wu, Caijun, Ma, Yunfeng, Jin, Yaofeng, Ji, Yanhong
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2016; Elsevier BV
• Subjects: 60 APPLIED LIFE SCIENCES; Animals; ANTIBODIES; Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - metabolism; Arthritis, Rheumatoid - pathology; CD4 T cell; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CELL PROLIFERATION; Cellular biology; COLLAGEN; Disease Models, Animal; ENZYME IMMUNOASSAY; Female; FLUIDS; FUNCTIONS; Humans; IMMUNOGLOBULINS; IN VIVO; INHIBITION; LYMPHOKINES; Male; MICE; Mice, Inbred BALB C; MOLECULES; PATHOGENESIS; PATIENTS; POLYMERASE CHAIN REACTION; Receptors, Immunologic - biosynthesis; Receptors, Immunologic - genetics; Receptors, Immunologic - immunology; RHEUMATIC DISEASES; Rheumatoid arthritis; Synovial fluid; Synovial Fluid - metabolism; TIGIT; TYROSINE; Up-Regulation - genetics; CD4 T cell; Synovial fluid; TIGIT; Rheumatoid arthritis
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2015.12.002

Rheumatoid arthritis (RA) is an immune-mediated disease with a pathogenesis that involves CD4 T cell activation. Multiple immune regulatory molecules expressed on CD4+ T cells were involved in RA pathogenesis. In this study, we investigated the role of T cell immunoglobulin and ITIM (immunoreceptor tyrosine-based inhibition motif) domain (TIGIT) in RA. The frequency of TIGIT-positive CD4+ T cells in the synovial fluid (SF) of active RA patients was lower than that of inactive RA patients. And a negative correlation between RA disease activity and TIGIT expression was found. In CD4+ T cells isolated from SF of active RA patients, TIGIT upregulation significantly decreased cell proliferation, as shown by MTT assay. TIGIT overexpression also significantly decreased the production of IFN-γ and IL-17, and increased that of IL-10, as determined by ELISA and qRT-PCR. In CD4+ T cells isolated from SF of inactive RA patients, TIGIT was silenced by siRNA transfection. As expected, TIGIT knockdown resulted in an opposite effect on cell proliferation and the production of cytokines, including IFN-γ, IL-17 and IL-10. A RA mouse model was established using type II collagen induction. TIGIT was upregulated in RA mouse by lentivector infection. As expected, TIGIT overexpression in vivo significantly alleviated the disease severity and deceased the levels of anti-collagen II antibodies. TIGIT upregulation in the early stage was more effective to alleviate disease severity. Our data suggested the potential therapeutic role of TIGIT in RA patients. •TIGIT expression on SF CD4+ T cells was decreased in active RA patients.•TIGIT overexpression diminished the function of CD4+ T cells.•TIGIT-siRNA transfection promotes the function of CD4+ T cells.•Mice with TIGIT overexpression were resistant to collagen induced RA.