IL-6-dependent and -independent pathways in the development of interleukin 17-producing T helper cells
IL-6-dependent and -independent pathways in the development of interleukin 17-producing T helper cells
复制标题
DOI：
10.1073/pnas.0705268104
复制
发表时间：
2007-07-17
影响因子：
11.1
通讯作者：
Kishimoto, Tadamitsu
中科院分区：
文献类型：
--
作者：
Kimura, Akihiro;Naka, Tetsuji;Kishimoto, Tadamitsu
CD4(+) T细胞产生IL-17[辅助性T (Th)17]，与Thl或Th2细胞不同，最近已被证明与自身免疫有关，但尚不完全清楚Th17细胞是如何从幼稚T细胞产生的。我们在这里证明，IL-6，而不是tnf - α或IL-1 β，可以与tgf - β联合诱导幼稚T细胞产生Th17细胞，并抑制tgf - β诱导的Foxp3表达。此外，由脂多糖刺激的骨髓源树突状细胞（DCCM）组成的条件培养基可以诱导幼稚T细胞产生IL-17。有趣的是，即使添加了抗gp 130抗体或IL-6 KO小鼠的DCCM， DCCM也能产生IL-17。IL-6和TGF-P的结合可以维持信号转导因子和转录激活因子Stat 3的激活，但不能维持Stat1的激活。在这些条件下，IL-27或ifn - γ抑制TGF-P + IL-6对Th17细胞的诱导，并维持Stat1的激活。相比之下，Stat1和Stat3在DCCM培养的初始T细胞中仍然被激活。这些发现代表了Th17从幼稚T细胞分化的不同基础。
CD4(+) T cells producing IL-17 [T helper (Th)17], as distinct from Thl or Th2 cells, have recently been shown to be associated with autoimmunity, but it is not entirely clear how Th17 cells are generated from naive T cells. We demonstrate here that IL-6, but not TNF-alpha or IL-1 beta, can, in combination with TGF-beta, induce Th17 cell generation from naive T cells and inhibit TGF-beta-induced Foxp3 expression. Moreover, conditioned medium from lipopolysaccharide-stimulated bone marrow-derived dendritic cells (DCCM) can induce IL-17 production in naive T cells. Interestingly, IL-17 was produced by DCCM even with the addition of anti-gp 130 antibody or DCCM from IL-6 KO mice. The combination of IL-6 and TGF-P could maintain activation of signal transducer and activator of transcription (Stat)3, but not of Stat1. IL-27 or IFN-gamma suppressed the induction of Th17 cells by TGF-P plus IL-6 and maintained Stat1 activation under these conditions. In contrast, both Stat1 and Stat3 remained to be activated in naive T cells cultured with DCCM. These findings represent a different basis for Th17 differentiation from naive T cells.