Imperial College London
Alternate

Dr Salvatore Papa

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Honorary Research Fellow
 
 
 
//

Contact

 

+44 (0)20 3313 8282s.papa

 
 
//

Location

 

10N.13Commonwealth BuildingHammersmith Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Tumanov:2009:10.1053/j.gastro.2008.09.015,
author = {Tumanov, AV and Koroleva, EP and Christiansen, PA and Khan, MA and Ruddy, MJ and Burnette, B and Papa, S and Franzoso, G and Nedospasov, SA and Fu, Y-X and Anders, RA},
doi = {10.1053/j.gastro.2008.09.015},
journal = {Gastroenterology},
pages = {694--704.e4},
title = {T cell-derived lymphotoxin regulates liver regeneration.},
url = {http://dx.doi.org/10.1053/j.gastro.2008.09.015},
volume = {136},
year = {2009}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BACKGROUND & AIMS: The ability of the liver to regenerate hepatic mass is essential to withstanding liver injury. The process of liver regeneration is tightly regulated by distinct signaling cascades involving components of the innate immune system, cytokines, and growth factors. However, the role of the adaptive immune system in regulation of liver regeneration is not well-defined. The role of adaptive immune system in liver regeneration was investigated in lymphocyte-deficient mice and in conditional lymphotoxin-deficient mice. METHODS: A model of liver regeneration after 70% partial hepatectomy was used, followed by examination of liver pathology, survival, DNA synthesis, and cytokine expression. RESULTS: We found that mice deficient in T cells show a reduced capacity for liver regeneration following partial hepatectomy. Furthermore, surface lymphotoxin, provided by T cells, is critical for liver regeneration. Mice specifically deficient in T-cell lymphotoxin had increased liver damage and a reduced capacity to initiate DNA synthesis after partial hepatectomy. Transfer of splenocytes from wild-type but not lymphotoxin-deficient mice improved liver regeneration in T cell-deficient mice. We found that an agonistic antibody against the lymphotoxin beta receptor was able to facilitate liver regeneration by reducing liver injury, increasing interleukin-6 production, hepatocyte DNA synthesis, and survival of lymphocyte-deficient (Rag) mice after partial hepatectomy. CONCLUSIONS: The adaptive immune system directly regulates liver regeneration via a T cell-derived lymphotoxin axis, and pharmacological stimulation of lymphotoxin beta receptor might represent a novel therapeutic approach to improve liver regeneration.
AU  - Tumanov,AV
AU  - Koroleva,EP
AU  - Christiansen,PA
AU  - Khan,MA
AU  - Ruddy,MJ
AU  - Burnette,B
AU  - Papa,S
AU  - Franzoso,G
AU  - Nedospasov,SA
AU  - Fu,Y-X
AU  - Anders,RA
DO  - 10.1053/j.gastro.2008.09.015
EP  - 704
PY  - 2009///
SP  - 694
TI  - T cell-derived lymphotoxin regulates liver regeneration.
T2  - Gastroenterology
UR  - http://dx.doi.org/10.1053/j.gastro.2008.09.015
UR  - https://www.ncbi.nlm.nih.gov/pubmed/18952083
VL  - 136
ER  -
Download