Contribution of the lymphotoxin β receptor to liver regeneration

Robert A. Anders, Sumit K. Subudhi, Jing Wang, Klaus Pfeffer, Yang Xin Fu

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1295-1300
Number of pages6
JournalJournal of Immunology
Volume175
Issue number2
StatePublished - Jul 15 2005

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Lymphotoxin-alpha
Liver Regeneration
Hepatectomy
Ligands
Receptors, Tumor Necrosis Factor, Member 14
Liver
Lymphocytes
T-Lymphocytes
Hepatomegaly
Herpesviridae
Liver Failure
DNA Damage
Hepatocytes
Glycoproteins
Homeostasis
Light
DNA
Proteins

ASJC Scopus subject areas

  • Immunology

Cite this

Anders, R. A., Subudhi, S. K., Wang, J., Pfeffer, K., & Fu, Y. X. (2005). Contribution of the lymphotoxin β receptor to liver regeneration. Journal of Immunology, 175(2), 1295-1300.

Contribution of the lymphotoxin β receptor to liver regeneration. / Anders, Robert A.; Subudhi, Sumit K.; Wang, Jing; Pfeffer, Klaus; Fu, Yang Xin.

In: Journal of Immunology, Vol. 175, No. 2, 15.07.2005, p. 1295-1300.

Research output: Contribution to journalArticle

Anders, RA, Subudhi, SK, Wang, J, Pfeffer, K & Fu, YX 2005, 'Contribution of the lymphotoxin β receptor to liver regeneration', Journal of Immunology, vol. 175, no. 2, pp. 1295-1300.
Anders RA, Subudhi SK, Wang J, Pfeffer K, Fu YX. Contribution of the lymphotoxin β receptor to liver regeneration. Journal of Immunology. 2005 Jul 15;175(2):1295-1300.
Anders, Robert A. ; Subudhi, Sumit K. ; Wang, Jing ; Pfeffer, Klaus ; Fu, Yang Xin. / Contribution of the lymphotoxin β receptor to liver regeneration. In: Journal of Immunology. 2005 ; Vol. 175, No. 2. pp. 1295-1300.
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