IL-6, IL-17 and STAT3: a holy trinity in auto-immunity?
IL-6, IL-17 and STAT3: a holy trinity in auto-immunity?
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DOI：
10.2741/4054
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发表时间：
2012-06-01
影响因子：
3.1
通讯作者：
Poli, Valeria
中科院分区：
文献类型：
--
作者：
Camporeale, Annalisa;Poli, Valeria
白细胞介素-6（IL-6）是一种多效性细胞因子，参与造血/免疫细胞和基质细胞之间的相互作用的调节，包括炎症的发生和消退、对感染的反应、组织重塑和癌症。它由成纤维细胞、内皮细胞、巨噬细胞和淋巴细胞等产生。IL-6可以与其配体结合受体IL-6 R α的膜结合和可溶形式相互作用，通过gp 130（IL-6受体复合物的信号传导亚基）的二聚化触发信号传导。这导致JAK/STAT途径的激活，并且主要在STAT 3转录因子的激活中达到高潮。IL-6和STAT 3最近都通过增强IL-6本身、IL-17和STAT 3的表达和/或活化的正反馈环而成为Th 17细胞分化和功能的主要调节剂。IL-6产生和信号传导失调与慢性炎性疾病、自身免疫和癌症相关，并且是作为有希望的治疗靶点的密集转化研究的对象。
Interleukin-6 (IL-6) is a pleiotropic cytokine involved in the regulation of the cross talk between haematopoietic/immune cells and stromal cells, including the onset and resolution of inflammation, responses to infection, tissue remodelling and cancer. It is produced, among others, by fibroblasts, endothelial cells, macrophages and lymphocytes. IL-6 can interact with both membrane-bound and soluble forms of its ligand-binding receptor, the IL-6Ralpha, triggering signalling via dimerization of gp130, the signalling subunit of the IL-6 receptor complex. This leads to the activation of the JAK/STAT pathway and mainly culminates in the activation of the STAT3 transcription factor. Both IL-6 and STAT3 have recently emerged as main regulators of the differentiation and function of Th17 cells, via a positive feedback loop enhancing expression and/or activation of IL-6 itself, IL-17 and STAT3. Dysregulated IL-6 production and signalling are associated with chronic inflammatory diseases, auto-immunity and cancer, and are the object of intense translational research as promising therapeutic targets.