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Regulation of liver regeneration by T cell‐ derived lymphotoxin
Author(s) -
Tumanov Alexei,
Christiansen Peter,
Koroleva Ekaterina,
Anders Robert,
Fu YangXin
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.465.8
Subject(s) - lymphotoxin , liver regeneration , regeneration (biology) , splenocyte , hepatectomy , immunology , microbiology and biotechnology , immune system , t cell , lymphocyte , biology , kupffer cell , chemistry , medicine , surgery , resection
The liver has a remarkable capacity to regenerate after injury or partial hepatectomy. The process of liver regeneration is tightly regulated by distinct signaling cascades involving components of innate immune system, cytokines and growth factors. However, the role of adaptive immune system in regulation of liver regeneration is not well defined. We found that mice deficient in T cells show a reduced capacity to regenerate after partial hepatectomy. We further demonstrate that surface Lymphotoxin (LT), a member of the TNF family of cytokines, provided by T cells is critical for liver regeneration. T cell‐specific LTβ deficient mice have increased liver damage and a reduced capacity to initiate DNA synthesis after partial hepatectomy. Transfer of splenocytes from wild type but not from LT deficient mice to lymphocyte deficient Rag mice improved liver regeneration. To develop a novel treatment to facilitate liver regeneration, we used an agonistic anti‐LTβR antibody which resulted in an increase in survival of Rag mice. Thus, our study revealed an unexpected role of lymphocyte‐restricted ligands in the control of liver regeneration.