title: Expression of human T cell immunoglobulin domain and mucin-3 (TIM-3) and TIM-3 ligands in peripheral blood from patients with systemic lupus erythematosus.
abstract: Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease. The T cell immunoglobulin and mucin domain (TIM) family is associated with autoimmune diseases, but its level of expression in the immune cells of patients with SLE is still uncertain. The aim of this study was to examine whether TIM-3 and Galectin-9 (Gal-9) contribute to the pathogenesis of SLE. In total, 30 patients with SLE and 30 healthy controls were recruited, and their levels of TIM-3 expression in peripheral blood mononuclear cells (PBMCs) were examined via flow cytometry. Meanwhile, the levels of Gal-9 expression in serum and in PBMCs were measured via an enzyme-linked immunosorbent assay (ELISA) kit and immunofluorescence staining, respectively. The relation between the level of TIM-3 or Gal-9 expression and the SLE disease activity index (SLEDAI) was also studied. Finally, the function of the TIM-3 and Gal-9 pathway in the pathogenesis of SLE was explored. Our results showed that the levels of expression of TIM-3 and Gal-9 on CD4(+) T cells, CD8(+) T cells, CD56(+) T cells and in serum in patients with SLE were significantly higher than those of healthy controls. We found that the level of Gal-9 expression was significantly higher in both serum and PMBCs of patients with SLE than in healthy controls. The up-regulation of TIM-3 and Gal-9 expression in patients with SLE was closely related to the SLEDAI scores. In addition, Gal-9 blocking antibody significantly inhibited CD3-stimulated PBMC proliferation and Th1-derived cytokines (IL-2, IFN-γ, and TNF-α), Th2-derived cytokines (IL-4, IL-10), a Th17-derived cytokine (IL-17A), and release of a pro-inflammatory factor (IL-6) in patients with SLE. The results suggest that increased expression of TIM-3 and Gal-9 may be a biomarker for SLE diagnosis and that the TIM-3 pathway may be a target for SLE treatment.
authors.affiliation: Clinical Immunology Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Road, Suzhou, 215006, China.|Department of Dermatology, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Jiao
authors.affiliation: Clinical Immunology Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Road, Suzhou, 215006, China.|Department of Dermatology, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Qihong
authors.initials: Q
authors.lastname: Qian
authors.affiliation: Department of Dermatology, First Hospital, Peking University, Beijing, 100034, China.
authors.forename: Zuotao
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Clinical Immunology Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Road, Suzhou, 215006, China.|Department of Dermatology, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Fumin
authors.initials: F
authors.lastname: Fang
authors.affiliation: Institute of Medical Biotechnology, Medical College of Soochow University, Suzhou, China.
authors.forename: Xiaohan
authors.initials: X
authors.lastname: Hu
authors.affiliation: Institute of Medical Biotechnology, Medical College of Soochow University, Suzhou, China.
authors.forename: Jingnan
authors.initials: J
authors.lastname: An
authors.affiliation: Clinical Immunology Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Road, Suzhou, 215006, China. njwujian@163.com.|Department of Rheumatology, The First Affiliated Hospital of Soochow University, 188 Shizi Road, Suzhou, 215006, China. njwujian@163.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.affiliation: Clinical Immunology Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Road, Suzhou, 215006, China. liucuiping@126.com.
authors.forename: Cuiping
authors.initials: C
authors.lastname: Liu
mesh_terms: D000328:Adult; D019138:Antibodies, Blocking / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D037161:Galectins / Q000819:agonists / Q000276:immunology / Q000378:metabolism*; D000072597:Hepatitis A Virus Cellular Receptor 2 / Q000819:agonists / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008297:Male; D008875:Middle Aged
chemical_list: D019138:Antibodies, Blocking; D016207:Cytokines; D037161:Galectins; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; C105032:LGALS9 protein, human; D008024:Ligands
keywords: Galectin-9 (Gal-9); Peripheral blood mononuclear cells (PBMCs); Systemic lupus erythematosus (SLE); T-cell immunoglobulin and mucin domain (TIM)