title: TIGIT overexpression diminishes the function of CD4 T cells and ameliorates the severity of rheumatoid arthritis in mouse models.
abstract: 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.
authors.affiliation: Department of Orthopedics, the 1st Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi Province, 710061, China. Electronic address: weigongzhao@126.com.
authors.forename: Weigong
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Immunology and Pathogenic Biology, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi Province, 710061, China.
authors.forename: Yanying
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Department of Immunology and Pathogenic Biology, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi Province, 710061, China.
authors.forename: Caijun
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Immunology and Pathogenic Biology, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi Province, 710061, China.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Pathology, the 2nd Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi Province, 710004, China.
authors.forename: Yaofeng
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Immunology and Pathogenic Biology, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi Province, 710061, China. Electronic address: yanhongjixian@163.com.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Ji
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology*; D013582:Synovial Fluid / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
chemical_list: D011971:Receptors, Immunologic; C534712:TIGIT protein, human
keywords: CD4 T cell; Rheumatoid arthritis; Synovial fluid; TIGIT