Discovery and initial characterization of Th9 cells: the early years
Discovery and initial characterization of Th9 cells: the early years
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DOI：
10.1007/s00281-016-0610-0
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发表时间：
2016
影响因子：
9
通讯作者：
E. Schmitt;T. Bopp
中科院分区：
文献类型：
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作者：
E. Schmitt;T. Bopp
Th 1/Th 2概念的提出代表了一个决定性的突破，涉及我们对功能不同的辅助性T细胞亚群如何通过分泌不同的细胞因子来调节非常多样化的免疫反应的理解。在这种情况下，IL-9被鉴定为除了Th 2细胞因子IL-4和IL-5之外还由T辅助细胞系产生。详细的分析显示，小鼠CD 4 +T辅助细胞的IL-9产生依赖于IL-2、IL-4和TGF-β的组合。大约十年后，人们发现TGF-β也可以诱导CD 4 +Treg细胞的发育。这一发现引发了一系列关于TGF-β对酪氨酸介导的T辅助细胞分化的中心作用的研究，这些研究阐明了IL-4抑制TGF-β的Treg细胞促进作用，而TGF-β损害IL-4的Th 2促进能力。相反，TGF-β与IL-4组合诱导优先产生IL-9的CD 4 +T辅助细胞的发育，并且其不同于最初被认为是IL-9的主要来源的Th 2细胞。此外，这种产生IL-9的CD 4 +T辅助细胞的过继转移显示出引起结肠炎和外周神经炎的发展。因此，独特的细胞因子表达模式与体内炎性表型相结合导致Th 9细胞被指定为新的CD 4 +T辅助细胞亚群。
The launch of the Th1/Th2 concept represented a decisive breakthrough concerning our understanding of how very diverse immune reactions can be regulated by functionally different T helper subpopulations via the secretion of different panels of cytokines. In this context, IL-9 was identified to be produced by T helper cell lines in addition to Th2 cytokines IL-4 and IL-5. Detailed analyses revealed that IL-9 production of mouse CD4+T helper cells was dependent on a combination of IL-2, IL-4, and TGF-β. Roughly a decade later, it was found that TGF-β can also induce the development of CD4+Treg cells. This finding engendered a series of studies on the central role of TGF-β for cytokine-mediated T helper cell differentiation which elucidated that IL-4 curbed the Treg cell-promoting effect of TGF-β while TGF-β impaired the Th2-promoting capacity of IL-4. Instead, TGF-β in combination with IL-4 induced the development of CD4+T helper cells that preferentially produced IL-9 and that were different from Th2 cells which originally were thought to be the main source of IL-9. In addition, adoptive transfer of such IL-9-producing CD4+T helper cells was shown to cause the development of colitis and peripheral neuritis. Hence, the unique cytokine expression pattern in combination with the inflammatory in vivo phenotype led to the designation of Th9 cells as a new CD4+T helper subpopulation.