title: TIGIT signalling pathway negatively regulates CD4+T-cell responses in systemic lupus erythematosus.
abstract: B-lymphocyte hyperactivity in systemic lupus erythematosus (SLE) is T-cell-dependent, and CD4+T-cell activation is essential to SLE pathogenesis. However, the mechanism of the deregulation of CD4+T cells in SLE is largely unknown. T-cell immunoglobulin and ITIM domain (TIGIT) is a new inhibitory receptor preferentially expressed on activated CD4+T cells. Here, we address the role of TIGIT in the pathogenesis of SLE. Our results showed that TIGIT expression on CD4+T cells was significantly elevated in patients with SLE and highly correlated with the activity of the disease. TIGIT+CD4+T cells from both healthy individuals and patients with SLE had a more activated phenotype than TIGIT-CD4+T cells. In contrast, the activation, proliferation and cytokine production potential of TIGIT+CD4+T cells were significantly lower than those of TIGIT-CD4+T cells. Furthermore, activation of the TIGIT pathway by using CD155 could substantially down-regulate the activities of CD4+T cells from SLE patients in vitro, and in vivo administration of CD155 resulted in a delayed development of SLE in MRL/lpr mice. TIGIT is a powerful negative regulator of CD4+T cells in SLE, which suggests that the TIGIT signalling pathway may be used as a potential therapeutic target for treating this disease.
authors.affiliation: Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Lie
authors.initials: L
authors.lastname: Mao
authors.affiliation: Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Hou
authors.affiliation: Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Shiji
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Liyan
authors.initials: L
authors.lastname: Mao
authors.affiliation: Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Munyemana Jean
authors.initials: MJ
authors.lastname: Bosco
authors.affiliation: Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Ziyong
authors.identifier: 0000-0003-2220-8497
authors.initials: Z
authors.lastname: Sun
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D016022:Case-Control Studies; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism* / Q000517:prevention & control; D008213:Lymphocyte Activation; D019463:Mice, Inbred MRL lpr; D010641:Phenotype; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism*; D011991:Receptors, Virus / Q000008:administration & dosage; D015398:Signal Transduction; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D011971:Receptors, Immunologic; D011991:Receptors, Virus; C556305:T cell Ig and ITIM domain protein, mouse; C534712:TIGIT protein, human; C066100:poliovirus receptor
keywords: 
  TIGIT
  ; CD4+ T cells; systemic lupus erythematosus; therapeutic target