TY - JOUR
T1 - Contribution of the lymphotoxin β receptor to liver regeneration
AU - Anders, Robert A.
AU - Subudhi, Sumit K.
AU - Wang, Jing
AU - Pfeffer, Klaus
AU - Fu, Yang Xin
PY - 2005/7/15
Y1 - 2005/7/15
N2 - The liver has an enormous capacity to regenerate in response to insults, but the cellular events and molecules involved in liver regeneration are not well denned. In this study, we report that ligands expressed on the surface of lymphocytes have a substantial effect on liver homeostasis. We demonstrate that a T cell-restricted ligand, homologous to lymphotoxin, exhibits inducible expression, competes with herpesvirus glycoprotein D for herpesvirus entry mediator on T cells (LIGHT), signaling through the lymphotoxin receptor (LTβR) expressed on mature hepatocytes induces massive hepatomegaly. Using genetic targeting and a receptor fusion protein, we further show that mice deficient in LTβR signaling have a severe defect in their ability to survive partial hepatectomy with marked liver damage and failure to initiate DNA synthesis after partial hepatectomy. We further show that mice deficient in a LTβR ligand, LTα, also show decreased ability to survive partial hepatectomy with similar levels of liver damage and decreased DNA synthesis. Therefore, our study has revealed an unexpected role of lymphocyte-restricted ligands and defined a new pathway in supporting liver regeneration.
AB - The liver has an enormous capacity to regenerate in response to insults, but the cellular events and molecules involved in liver regeneration are not well denned. In this study, we report that ligands expressed on the surface of lymphocytes have a substantial effect on liver homeostasis. We demonstrate that a T cell-restricted ligand, homologous to lymphotoxin, exhibits inducible expression, competes with herpesvirus glycoprotein D for herpesvirus entry mediator on T cells (LIGHT), signaling through the lymphotoxin receptor (LTβR) expressed on mature hepatocytes induces massive hepatomegaly. Using genetic targeting and a receptor fusion protein, we further show that mice deficient in LTβR signaling have a severe defect in their ability to survive partial hepatectomy with marked liver damage and failure to initiate DNA synthesis after partial hepatectomy. We further show that mice deficient in a LTβR ligand, LTα, also show decreased ability to survive partial hepatectomy with similar levels of liver damage and decreased DNA synthesis. Therefore, our study has revealed an unexpected role of lymphocyte-restricted ligands and defined a new pathway in supporting liver regeneration.
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U2 - 10.4049/jimmunol.175.2.1295
DO - 10.4049/jimmunol.175.2.1295
M3 - Article
C2 - 16002734
AN - SCOPUS:23244437984
SN - 0022-1767
VL - 175
SP - 1295
EP - 1300
JO - Journal of Immunology
JF - Journal of Immunology
IS - 2
ER -