title: Galectin-9 ameliorates Con A-induced hepatitis by inducing CD4(+)CD25(low/int) effector T-Cell apoptosis and increasing regulatory T cell number.
abstract: BACKGROUND
  T cell-mediated liver damage is a key event in the pathogenesis of many chronic human liver diseases, such as liver transplant rejection, primary biliary cirrhosis, and sclerosing cholangitis. We and other groups have previously reported that galectin-9, one of the β-galactoside binding animal lectins, might be potentially useful in the treatment of T cell-mediated diseases. To evaluate the direct effect of galectin-9 on hepatitis induced by concanavalin A (Con A) administration in mice and to clarify the mechanisms involved, we administered galectin-9 into mice, and evaluated its therapeutic effect on Con A-induced hepatitis.
  
  
  RESULTS
  Galectin-9 was administrated i.v. to Balb/c mice 30 min before Con A injection. Compared with no treatment, galectin-9 pretreatment significantly reduced serum ALT and AST levels and improved liver histopathology, suggesting an ameliorated hepatitis. This therapeutic effect was not only attributable to a blunted Th1 immune response, but also to an increased number in regulatory T cells, as reflected in a significantly increased apoptosis of CD4(+)CD25(low/int) effector T cells and in reduced proinflammatory cytokine levels.
  
  
  CONCLUSIONS
  Our findings constitute the first preclinical data indicating that interfering with TIM-3/galectin-9 signaling in vivo could ameliorate Con A-induced hepatitis. This strategy may represent a new therapeutic approach in treating human diseases involving T cell activation.
authors.affiliation: Central Laboratory of Yijishan Hospital, Wannan Medical College, Wuhu, People's Republic of China. lvkun315@126.com
authors.forename: Kun
authors.initials: K
authors.lastname: Lv
authors.forename: Yingying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Mengying
authors.initials: M
authors.lastname: Zhang
authors.forename: Min
authors.initials: M
authors.lastname: Zhong
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Suo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D018791:CD4 Lymphocyte Count; D003208:Concanavalin A / Q000009:adverse effects*; D016207:Cytokines / Q000096:biosynthesis; D037161:Galectins / Q000494:pharmacology* / Q000627:therapeutic use; D006505:Hepatitis / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D037161:Galectins; D053645:Interleukin-2 Receptor alpha Subunit; D003208:Concanavalin A