Role of gamma-delta T cells in liver inflammation and fibrosis.
Role of gamma-delta T cells in liver inflammation and fibrosis.
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DOI：
10.4291/wjgp.v5.i2.107
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发表时间：
2014-05-15
期刊：
影响因子：
--
通讯作者：
Tacke, Frank
中科院分区：
文献类型：
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作者：
Hammerich, Linda;Tacke, Frank
传统的适应性T细胞反应有助于肝脏炎症和纤维化，特别是在慢性病毒感染和自身免疫性肝炎中。然而，非常规γ-δ（γ δ）T细胞在肝脏疾病中的作用尚不清楚。在过去的二十年中，越来越多的证据表明，在小鼠和人类的各种炎症条件下，肝脏中的γ δ T细胞数量显着增加。最近的研究表明，γ δ T细胞对肝脏疾病进展的功能作用取决于所涉及的亚群，其可以通过不同T细胞受体链和特定细胞因子的表达来鉴定。有趣的是，γ δ T细胞在肝脏疾病中可能具有保护性和致病性功能。例如，产生干扰素γ的γ δ T细胞诱导肝细胞以及肝肿瘤细胞的凋亡;而表达白介素-17的γ δ T细胞可以下调其他免疫细胞的致病效应子功能，并可以促进纤维化星状细胞的凋亡。然而，在人类肝病以及小鼠模型中获得的结果目前还不完全确定，γ δ T细胞对肝病结果的影响可能因病因和疾病阶段而异。进一步定义参与急性和慢性肝脏炎症的γ δ T细胞亚群及其效应细胞因子可能会揭示干扰γ δ T细胞是否可以成为治疗肝脏疾病的有用靶点。
Conventional adaptive T cell responses contribute to liver inflammation and fibrogenesis, especially in chronic viral infections and autoimmune hepatitis. However, the role of unconventional gamma-delta (gammadelta) T cells in liver diseases is less clear. In the past two decades, accumulating evidence revealed that gammadelta T cell numbers remarkably increase in the liver upon various inflammatory conditions in mice and humans. More recent studies demonstrated that the functional effect of gammadelta T cells on liver disease progression depends on the subsets involved, which can be identified by the expression of distinct T cell receptor chains and of specific cytokines. Fascinatingly, gammadelta T cells may have protective as well as pathogenic functions in liver diseases. Interferon gamma-producing gammadelta T cells, for example, induce apoptosis in hepatocytes but also in hepatic tumor cells; while interleukin-17-expressing gammadelta T cells can downregulate pathogenic effector functions of other immune cells and can promote apoptosis of fibrogenic stellate cells. However, the results obtained in human liver disease as well as murine models are not fully conclusive at present, and the effects of gammadelta T cells on the outcome of liver disease might vary dependent on etiology and stage of disease. Further definitions of the gammadelta T cell subsets involved in acute and chronic liver inflammation, as well as their effector cytokines might uncover whether interference with gammadelta T cells could be a useful target for the treatment of liver disease.