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首页> 外文期刊>Hepatology: Official Journal of the American Association for the Study of Liver Diseases >B7-H4 mediates inhibition of T cell responses by activated murine hepatic stellate cells.
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B7-H4 mediates inhibition of T cell responses by activated murine hepatic stellate cells.

机译:B7-H4介导活化的鼠肝星状细胞对T细胞反应的抑制。

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摘要

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.
机译:肝纤维化是由肝星状细胞(HSC)从静止状态转变为活化状态所介导的。为了了解HSC在肝脏免疫中的作用,我们研究了这种转变对体外T细胞刺激的影响。与静止的HSC不同,活化的HSC不会诱导抗原特异性T细胞的增殖。静态和激活的HSC的表型分析表明,激活的HSC表达了共抑制分子B7-H4。通过激活的HSC中的小干扰RNA(siRNA)沉默B7-H4,可恢复T细胞增殖,分化和恢复效应物召回反应的能力。此外,HSC上B7-H4的表达抑制了早期T细胞活化,外源白介素(IL)-2的添加逆转了活化HSC诱导的T细胞无反应性。结论:这些研究揭示了活化的HSC通过共抑制分子B7-H4的表达在减轻肝内T细胞反应中的新作用,并可能为肝纤维化过程中的肝内免疫学提供基础见解。

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