Liver sinusoidal endothelial cell lectin, LSECtin, negatively regulates hepatic T-cell immune response.
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.
Tang
Li
L
State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China.
Yang
Juntao
J
Liu
Wanli
W
Tang
Xiaoming
X
Chen
Jie
J
Zhao
Dianyuan
D
Wang
Min
M
Xu
Feng
F
Lu
Yantao
Y
Liu
Biao
B
Sun
Qihong
Q
Zhang
Lingqiang
L
He
Fuchu
F
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
C505228:CLEC4G protein, human; D037181:Lectins, C-Type; D011134:Polysaccharides; D011993:Recombinant Fusion Proteins; D003208:Concanavalin A