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Deficiency in CD1d Enhances Cholestasis‐induced Hepatic Tissue Injury and Fibrosis
Author(s) -
Hines Ian Neil,
Kremer Michael,
Milton Richard Jameson,
Perry Ashley Marie,
Wheeler Michael Daryl
Publication year - 2006
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.20.4.a631-b
Subject(s) - cd1d , natural killer t cell , liver injury , cholestasis , fibrosis , medicine , immune system , endocrinology , biology , immunology , t cell
T cells are associated with the development of hepatic fibrosis. CD1d‐restricted natural killer T (NKT) cells represent 25% of resident hepatic lymphocytes and regulate the activity of both resident and infiltrating T cells. The purpose of the current study was to investigate the role of NKT cells activated by CD1d in the development of cholestatic liver injury. Male Balb/c wild type (wt) mice or CD1d‐deficient (CD1d −/− ) mice, which lack functional NKT cells, were subjected to ligation of the common bile duct (BDL) or sham surgery for 21 days. Wt mice subjected to BDL showed significant liver injury as assessed by serum aspartate aminotransferase (AST) levels (126.7±7.1 vs 835.2±77.1 for sham vs BDL respectively; p<0.05), tissue collagen deposition, tumor necrosis factor alpha (TNFα) and transforming growth factor beta 1 (TGFβ1) expression and periportal CD3 + T cell accumulation when compared to their sham operated controls. BDL in CD1d −/− mice caused a significant increase in serum AST (835.2±77.1 vs. 1544.4±312.2 for wt vs CD1d −/− mice subjected to BDL respectively; p<0.05) compared to wt mice under similar conditions. Tissue collagen and T cell accumulation were also significantly enhanced in CD1d −/− following BDL in comparison to wt mice. These changes were observed despite no differences in TNFα and TGFβ following BDL. In summary, absence of CD1d enhanced cholestatic liver injury and fibrosis possibly through increased T cell recruitment. CD1d‐reactive NKT cells may represent an important regulator of the immune response in the setting of fibrotic liver disease. This work was supported by NIAAA grants AA014243 and F32‐AA015005.