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B7‐H4 mediates inhibition of T cell responses by activated murine hepatic stellate cells
Author(s) -
Chinnadurai Raghavan,
Grakoui Arash
Publication year - 2010
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.23953
Subject(s) - hepatic stellate cell , microbiology and biotechnology , biology , gene silencing , t cell , liver cytology , immune system , immunology , gene , endocrinology , biochemistry , liver metabolism
Liver fibrosis is mediated by the transformation of hepatic stellate cells (HSC) from a quiescent to an activated state. To understand the role of HSC in liver immunity, we investigated the effect of this transition on T cell stimulation in vitro. Unlike quiescent HSC, activated HSC did not induce proliferation of antigen‐specific T cells. Phenotypic analysis of quiescent and activated HSC revealed that activated HSC expressed the coinhibitory molecule B7‐H4. Silencing B7‐H4 by small interfering RNA (siRNA) in activated HSC restored the ability of T cells to proliferate, differentiate, and regain effector recall responses. Furthermore, expression of B7‐H4 on HSC inhibits early T cell activation and addition of exogenous interleukin (IL)‐2 reversed the T cell anergy induced by activated HSC. Conclusion: These studies reveal a novel role for activated HSC in the attenuation of intrahepatic T cell responses by way of expression of the coinhibitory molecule B7‐H4, and may provide fundamental insight into intrahepatic immunity during liver fibrogenesis. (H EPATOLOGY 2010)