IL-33/ST2 signaling in liver transplantation
IL-33/ST2 signaling in liver transplantation
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DOI：
10.1038/s41423-020-0418-7
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发表时间：
2020-10
影响因子：
24.1
通讯作者：
Z. Tan;Beicheng Sun
中科院分区：
文献类型：
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作者：
Z. Tan;Beicheng Sun
在发表在《细胞与分子免疫学》上的一项研究中，我们描述了一种新的机制，IL-33通过MAPK途径驱动肝纤维化。该研究表明，肝细胞衍生的IL-33在胆管结扎（BDL）诱导的肝损伤和纤维化后升高，并以JNK/ERK/p38依赖性方式激活肝星状细胞。1作为IL-1家族的成员，IL-33通过IL-4、IL-6和IL-10的产生促进CD 4 + T辅助细胞2（Th 2）细胞因子，但抑制Th 1细胞因子。Th细胞是通过在组织中释放不同类型的细胞因子来激活和抑制B细胞和细胞毒性T细胞的适应性免疫应答的中心。这些调节对于免疫稳态和抑制针对自身抗原的过度反应以防止自身免疫是必不可少的。肝移植手术是一个复杂的过程，伴随着移植物或主要器官的缺血-再灌注，危及生命的出血，和稳态不稳定。患有病毒性肝炎、酒精性肝炎或肝癌的受体可能有潜在的肝脏炎症，细胞因子分泌增加可能导致移植物排斥。本文将重点介绍IL-33/ST 2信号转导在肝移植中的重要作用，并强调干预ST 2/IL-33信号转导作为一种治疗选择的潜力。以前的报道表明，IL-33在小鼠和人类的多种器官和细胞类型中一致表达，特别是在成纤维细胞、上皮细胞、高内皮微静脉和肝细胞的细胞核中。2.免疫荧光显示，IL-33在白蛋白标记的肝细胞中持续表达，而在CK-19阳性的胆管细胞和GFAP阳性的肝星状细胞中则不表达。在组织损伤时，IL-33立即释放到细胞外空间中，并在急性组织损伤期间充当警报素。膜结合的ST 2激活MyD 88/NF-κB信号通路，促进Th 2、调节性T细胞（Treg）和先天性淋巴细胞2型功能，这些功能调节晚期免疫应答并增强或抑制炎症反应（图1）。
In a study published in Cellular & Molecular Immunology, we described a novel mechanism by which IL-33 drives hepatic fibrosis through the MAPK pathway. The study demonstrated that hepatocyte-derived IL-33 is elevated upon bile duct ligation (BDL)-induced liver injury and fibrogenesis and activates hepatic stellate cells in a JNK/ERK/p38-dependent manner. 1 As a member of the IL-1 family, IL-33 promotes CD4+ T helper 2 (Th2) cytokines but suppresses Th1 cytokines via IL-4, IL-6, and IL-10 production. Th cells are central to the adaptive immune response activation and suppression of B cells and cytotoxic T cells by releasing different types of cytokines in tissues. These regulations are essential for immune homeostasis and suppression of excessive response against self-antigens to prevent autoimmunity. Liver transplantation surgery is a complex procedure accompanied by graft or major organ ischemia-reperfusion, life-threatening hemorrhage, and homeostasis instability. Recipients with viral hepatitis, alcoholic hepatitis, or hepatic carcinoma could have underlying liver inflammation, and increased secretion of cytokines may result in graft rejection. This commentary will focus on the crucial role of IL-33/ST2 signaling in liver transplantation and highlight the potential of intervening in ST2/IL-33 signaling as a treatment option.Previous reports suggested that IL-33 is consistently expressed by multiple organs and cell types in mice and humans, particularly in the nuclei of fibroblasts, epithelial cells, high endothelial venules, and hepatocytes. 2 Using immunofluorescence, we also demonstrated that IL-33 is consistently expressed in albuminlabeled hepatocytes other than CK-19-positive cholangiocytes or GFAP-positive hepatic stellate cells during BDL-associated liver damage. Upon tissue damage, IL-33 is immediately released into the extracellular space and acts as an alarmin during acute tissue injury. Membrane-bound ST2 activates the MyD88/NF-κB signaling pathway, contributing to Th2, regulatory T cell (Treg), and innate lymphoid cell type 2 functions, which regulate late immune responses and enhance or suppress inflammatory reactions (Fig. 1).