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机构地区:[1]军事医学科学院基础医学研究所分子免疫室,北京100850
出 处:《生物化学与生物物理进展》2008年第2期117-123,共7页Progress In Biochemistry and Biophysics
基 金:国家重点基础研究发展计划(973)资助项目(2007C512406);国家自然科学基金资助项目(30571732)~~
摘 要:Th17细胞作为一个不同于Th1、Th2的细胞亚群,已经被证实在自身免疫病、感染等疾病中发挥重要的作用.为了进一步认识Th17细胞的效应机制,近来对于Th17细胞的分化及调节进行了深入的研究,证实TGF-β与IL-6或者IL-21的协同作用是诱导Th17细胞分化的关键因素,而IL-23在促进IL-17分泌,增强Th17细胞效应功能方面发挥重要作用.与Th1、Th2、Treg细胞特异性的转录调节因子T-bet、GATA3、Foxp3相对应,现证实ROR-γt(retinoid-related orphan receptors-γt)是促进Th17细胞分化、调节其功能的特异性转录调节因子.Th17细胞通过分泌IL-17A、IL-17F、IL-21、IL-22、IL-6、TNF-α等细胞因子发挥效应功能。其中IL-21作为Th17细胞的一个自分泌调节因子,在诱导Th17分化、抑制Th1、Treg功能方面发挥关键作用.而另一方面,近来发现,重要的T细胞生长因子IL-2在维持、促进Th1、Th2、Treg及CD8+T细胞功能活性的同时,却发挥着抑制Th17细胞分化的作用.Th1、Treg、Th17细胞的分化之间存在微妙的调节关系,TGF-β的水平、作用的时间决定着上述三群T细胞的分化结局.Th17细胞与Th1细胞均是自身免疫病及感染性疾病的重要效应细胞,二者的作用是否有时间、空间、功能方面的特异性?TGF-β如何调节两群效应细胞的分化方向及功能?以及Th17细胞在体内免疫平衡中的作用,是否可以通过Th17细胞诱导免疫耐受等,是人们急于回答的非常有意义的课题.As a new identified help T cell lineage different from Th1 and Th2 cells, Th17 cell has been found played important roles in the pathogenesis of autoimmunity and inflammatory disease. To further identify their roles, the differentiation and regulation of Th17 cells has been widely explored recently. Now it has been confirmed that TGF-beta, combined with IL-6 or IL-21, play critical roles in the differentiation of Th17 cells. While IL-23 mainly contribute in promoting the secretion of IL-17 and maintaining the function of Th1 7 cells. Corresponding with the Th1,Th2, and Treg cells, which has special transcription factors T-bet, GATA3, Foxp3 respectively, now it has been confirmed that ROR-γt (retinoid-related orphan receptors-γt) is the special transcription factor which specially regulate the differentiation of Th17 cells. Th17 cells function through their secreted pro-inflammatory cytokines, including IL-17A, IL-17F, IL-21, IL-22, IL-6, TNF-α. Among them IL-21, which act as a autocrine cytokine of Th17 cells, play critical roles in promoting the differentiation of Th17 cells while inhibiting the differentiation and function of Th1 and Treg cells. On the other hand, IL-2, which is obligatory for the growth of Th1,Th2,Treg and CD8^+T cells, now has been found negatively regulate the differentiation of Th17 cells. In all, differentiation of Th17 and Treg, Th1 cells are exactly regulated in vivo, in which TGF-beta played critical roles. As both Th1 and Th17 cells participate in the pathogenesis of autoimmunity and inflammatory diseases, are they play synergistic roles or function at different time point or location? How TGF-β regulate Th17 and Treg cells? Can Th17 cells be used as a target for immune tolerance induction? All above questions will certainly be of continuing interest.
分 类 号:R26[医药卫生—中医外科学]
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