A novel heterodimeric cytokine consisting of IL-17 and IL-17F regulates inflammatory responses
A novel heterodimeric cytokine consisting of IL-17 and IL-17F regulates inflammatory responses
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DOI：
10.1038/cr.2007.35
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发表时间：
2007-05-01
期刊：
影响因子：
44.1
通讯作者：
Dong, Chen
中科院分区：
文献类型：
--
作者：
Chang, Seon Hee;Dong, Chen
CD 4+辅助性T（TH）细胞在免疫应答中起关键作用。最近，一种新的TH细胞亚群，称为蒂尔-17、TH 17或炎性TH（THi），已被鉴定为组织炎症的关键介质。这些细胞产生IL-17（也称为IL-17 A）和IL-17 F，这两种最同源的细胞因子共享相似的调节。在这里，我们报告了当在293 T细胞中过表达时，IL-17和IL-17 F不仅形成同源二聚体，而且形成异源二聚体，我们将其命名为IL-17 A/F。完全分化的小鼠THi细胞还天然分泌IL-17 A/F以及IL-17和IL-17 F同型二聚体细胞因子。与同型二聚体细胞因子相比，重组IL-17 A/F蛋白在诱导IL-6和KC（CXCL 1）方面表现出中等水平的效力。IL-17 A/F对IL-6和KC表达的调节依赖于IL-17 RA和TRAF 6。因此，IL-17 A/F细胞因子代表了T细胞调节炎症反应的另一种机制，并可作为治疗各种免疫介导疾病的新靶点。
CD4+ helper T (TH) cells play crucial roles in immune responses. Recently a novel subset of TH cells, termed THIL-17, TH17 or inflammatory TH (THi), has been identified as critical mediators of tissue inflammation. These cells produce IL-17 (also called IL-17A) and IL-17F, two most homologous cytokines sharing similar regulations. Here we report that when overexpressed in 293T cells, IL-17 and IL-17F form not only homodimers but also heterodimers, which we name as IL-17A/F. Fully differentiated mouse THi cells also naturally secrete IL-17A/F as well as IL-17 and IL-17F homodimeric cytokines. Recombinant IL-17A/F protein exhibits intermediate levels of potency in inducing IL-6 and KC (CXCL1) as compared to homodimeric cytokines. IL-17A/F regulation of IL-6 and KC expression is dependent on IL-17RA and TRAF6. Thus, IL-17A/F cytokine represents another mechanism whereby T cells regulate inflammatory responses and may serve as a novel target for treating various immune-mediated diseases.