Immunomodulatory effects of transforming growth factor-beta in the liver.
Immunomodulatory effects of transforming growth factor-beta in the liver.
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DOI：
10.3978/j.issn.2304-3881.2014.11.06
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发表时间：
2014-12-01
影响因子：
8
通讯作者：
Weiskirchen, Ralf
中科院分区：
文献类型：
--
作者：
Schon, Hans-Theo;Weiskirchen, Ralf
转化生长因子-β (TGF-β) 家族的成员是有效的调节细胞因子，可影响免疫系统的多种细胞类型，介导促炎或抗炎反应。在肝脏中，TGF-β由大量非实质肝细胞产生，包括肝星状细胞 (HSC)、肝窦内皮细胞 (LSEC)、库普弗细胞 (KC) 和树突状细胞 (DC) 以及其他肝淋巴细胞中的自然杀伤 (NK) T 细胞。 TGF-β 对其他细胞的影响非常广泛。它与其他可溶性因子一起控制各种 T 细胞亚群的成熟、分化和活性，从而预防或引发感染、移植物抗宿主反应、免疫疾病和癌症形成。在过去的几十年中，一些 TGFB1 多态性与肝脏疾病的发病机制相关，并且血浆 TGF-β 是检测肝脏病变的合适生物标志物，这一点变得越来越明显。此外，由于TGF-β能够影响T细胞亚群的数量和质量及其活性，因此显然平衡的TGF-β活性对于肝脏稳态至关重要。在本综述中，我们重点介绍了 TGF-β 在肝脏免疫生物学中的一些关键功能。我们讨论了它对适应性免疫的调节功能、对各种 T 细胞亚群分化的影响、它与 Toll 样受体信号传导的串扰，以及它对肝脏功能损伤的贡献。
Members of the transforming growth factor-beta (TGF-beta) family are potent regulatory cytokines that affect multiple cell types of the immune system mediating pro-inflammatory or anti-inflammatory responses. In the liver, TGF-beta is produced by a multitude of non-parenchymal liver cells including hepatic stellate cells (HSCs), liver sinusoidal endothelial cells (LSECs), Kupffer cells (KCs), and dendritic cells (DCs) as well as natural killer (NK) T cells among other hepatic lymphocytes. The effect of TGF-beta on other cells is highly versatile. In concert with other soluble factors, it controls the maturation, differentiation and activity of various T cell subsets that either prevent or actuate infections, graft-versus-host reactions, immune diseases, and cancer formation. During the last decades, it became evident that some TGFB1 polymorphisms are associated with the pathogenesis of hepatic disease and that plasma TGF-beta is a suitable biomarker to detect liver lesions. Moreover, since TGF-beta has capacity to influence the quantity and quality of T cell subsets as well as their activity, it is obvious that a well-balanced TGF-beta activity is essential for liver homeostasis. In the present review, we highlight some pivotal functions of TGF-beta in hepatic immunobiology. We discuss its regulatory function on adaptive immunity, the impact on differentiation of various T cell subsets, its crosstalk with Toll like receptor signaling, and its contribution to functional impairment of the liver.