title: Elevated Galectin-9 Suppresses Th1 Effector Function and Induces Apoptosis of Activated CD4+T Cells in Osteoarthritis.
abstract: T cell immunoglobulin and mucin domain 3 (Tim-3) is a critical regulatory molecule found on activated Th1 cells, exhausted CD8+T cells, and resting monocytes/macrophages. Galectin-9 (Gal-9) is an identified ligand for Tim-3. Interaction between Tim-3 and Gal-9 is thought to inhibit Th1 responses. The regulation and function of Tim-3 and Gal-9 in osteoarthritis (OA) have not been intensively investigated. We found that in peripheral blood, CD4+T cells, but not CD8+T cells or CD14+monocytes, from OA patients presented significantly elevated Tim-3 and Gal-9 expression compared to those from healthy controls (HC). The CD4+T cells from OA did not present altered Th1, Th2, and Th17 composition in the peripheral blood, but secreted less Th1 cytokine interleukin 2 (IL-2) and interferon gamma (IFN-γ) after activation. Further investigation demonstrated that Gal-9 induced high levels of apoptosis in activated CD4+T cells from OA patients. Inhibition of Gal-9 resulted in significantly higher IL-2 and IFN-γ expression that was directly correlated with the number of non-apoptotic cells. In the synovial fluid, both secreted Gal-9 and surface Gal-9 levels were significantly higher in less-severe grade 2 OA patients than in more-severe grade 4 OA patients. Surface Tim-3 was also higher in synovial fluid CD8+T cells and CD14+monocytes from grade 2 OA patients and lower in grade 4 OA patients. Together, these results suggested that Tim-3 and Gal-9 could downregulate T cell inflammation in OA, and could be utilized as a novel therapeutic strategy.
authors.affiliation: Department of Orthopedics, Bayi Hospital Affiliated Nanjing University of Chinese Medicine, 34 Yanggongjing Road, Nanjing, Jiangsu, 210002, People's Republic of China.
authors.forename: Shufeng
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Orthopedics, Bayi Hospital Affiliated Nanjing University of Chinese Medicine, 34 Yanggongjing Road, Nanjing, Jiangsu, 210002, People's Republic of China.
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Xiamen University Affiliated Chenggong Hospital, Xiamen, Fujian, 361000, People's Republic of China.
authors.forename: Fengrong
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Orthopedics, Bayi Hospital Affiliated Nanjing University of Chinese Medicine, 34 Yanggongjing Road, Nanjing, Jiangsu, 210002, People's Republic of China.
authors.forename: Guoyin
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Outpatient, Jinling Hospital, Nanjing University School of Medicine, 305 Zhongshan East Road, Nanjing, Jiangsu, 210002, People's Republic of China. wengzhiqiang9898@sina.com.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Weng
authors.affiliation: Department of Orthopedics, Bayi Hospital Affiliated Nanjing University of Chinese Medicine, 34 Yanggongjing Road, Nanjing, Jiangsu, 210002, People's Republic of China. jianminchen_nj@126.com.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Chen
mesh_terms: D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D037161:Galectins / Q000502:physiology*; D000072597:Hepatitis A Virus Cellular Receptor 2 / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000517:prevention & control; D008213:Lymphocyte Activation / Q000276:immunology*; D010003:Osteoarthritis / Q000276:immunology* / Q000473:pathology; D018417:Th1 Cells / Q000502:physiology*
chemical_list: D037161:Galectins; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; C105032:LGALS9 protein, human
keywords: Tim-3; galectin-9; osteoarthritis