T Cell-Derived Lymphotoxin Regulates Liver Regeneration

Alexei V. Tumanov, Ekaterina P. Koroleva, Peter A. Christiansen, Mehtab A. Khan, Matthew J. Ruddy, Byron Burnette, Salvatore Papa, Guido Franzoso, Sergei A. Nedospasov, Yang Xin Fu, Robert A. Anders

Producción científica: Articlerevisión exhaustiva

59 Citas (Scopus)

Resumen

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 β 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 β receptor might represent a novel therapeutic approach to improve liver regeneration.

Idioma originalEnglish (US)
Páginas (desde-hasta)694-704.e4
PublicaciónGastroenterology
Volumen136
N.º2
DOI
EstadoPublished - feb 2009
Publicado de forma externa

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

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