title: Liver sinusoidal endothelial cell lectin, LSECtin, negatively regulates hepatic T-cell immune response.
abstract: OBJECTIVE
  The liver is an organ with paradoxic immunologic properties and is known for its tolerant microenvironment, which holds important implications for hepatic diseases. The molecular basis for this local immune suppression, however, is poorly understood. In this study, we aimed to determine the role of liver sinusoidal endothelial cell lectin (LSECtin), a recently identified member of the dendritic cell-specific ICAM-3 grabbing nonintegrin (DC-SIGN) family, in the regulation of hepatic T-cell immune response.
  
  
  METHODS
  The regulation of T-cell effector function by LSECtin was determined by co-stimulated T cells with anti-CD3/CD28 monoclonal antibody and LSECtin protein, or co-culture of T-cell receptor transgenic T cells with mouse LSECs in vitro. We generated LSECtin knockout mice and prepared recombinant LSECtin protein and complementary DNA plasmids to analyze the role of LSECtin in hepatic T-cell immune regulation in vivo.
  
  
  RESULTS
  We showed that LSECtin specifically recognized activated T cells and negatively regulated their immune responses. In mice with T-cell-mediated acute liver injury, the lack of LSECtin accelerated the disease owing to an increased T-cell immune response, whereas the exogenous administration of recombinant LSECtin protein or plasmid ameliorated the disease via down-regulation of T-cell immunity.
  
  
  CONCLUSIONS
  Our results reveal that LSECtin is a novel regulator of T cells and expose a crucial mechanism for hepatic T-cell immune suppression, perhaps opening up a new approach for treatment of inflammatory diseases in the liver.
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Tang
authors.forename: Juntao
authors.initials: J
authors.lastname: Yang
authors.forename: Wanli
authors.initials: W
authors.lastname: Liu
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Tang
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Dianyuan
authors.initials: D
authors.lastname: Zhao
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.forename: Yantao
authors.initials: Y
authors.lastname: Lu
authors.forename: Biao
authors.initials: B
authors.lastname: Liu
authors.forename: Qihong
authors.initials: Q
authors.lastname: Sun
authors.forename: Lingqiang
authors.initials: L
authors.lastname: Zhang
authors.forename: Fuchu
authors.initials: F
authors.lastname: He
mesh_terms: D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D049109:Cell Proliferation; D018920:Coculture Techniques; D003208:Concanavalin A; D006224:Cricetinae; D003412:Cricetulus; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000276:immunology* / Q000473:pathology; D015316:Genetic Therapy; D018922:HL-60 Cells; D006520:Hepatitis, Animal / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D006801:Humans; D007108:Immune Tolerance; D019169:Jurkat Cells; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000098:blood supply / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011134:Polysaccharides / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D014162:Transfection; D020298:U937 Cells
chemical_list: C505228:CLEC4G protein, human; D037181:Lectins, C-Type; D011134:Polysaccharides; D011993:Recombinant Fusion Proteins; D003208:Concanavalin A