Th17 Cells and autoimmune encephalomyelitis (EAE/MS).
Th17 Cells and autoimmune encephalomyelitis (EAE/MS).
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DOI：
10.2332/allergolint.r-07-159
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发表时间：
2008-06-01
期刊：
影响因子：
--
通讯作者：
Yamamura, Takashi
中科院分区：
文献类型：
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作者：
Aranami, Toshimasa;Yamamura, Takashi
多发性硬化（MS）是一种影响中枢神经系统的CD 4 + T细胞介导的自身免疫性疾病。人们普遍认为，IL-12驱动的Th 1细胞是人类MS和实验性自身免疫性脑脊髓炎（MS的动物模型）中的致病性T细胞。最近的数据已经确定，IL-23驱动的产生IL-17的CD 4 + T细胞（称为Th 17细胞）在EAE的发病机制中起着关键作用。TGF-β和IL-6的组合通过转录因子ROR γ mat的表达诱导Th 17细胞谱系定型。Th 17细胞和诱导的Foxp 3 + T调节细胞在由TGF-β和IL-6控制的T细胞谱系定型中处于相互位置。维生素A代谢物视黄酸通过Foxp 3的TGF-β依赖性诱导参与该过程。我们已经证明，人Th 17细胞可以被鉴定为CCR 2 + CCR 5-记忆性CD 4 + T细胞。IL-23/Th 17轴在包括MS在内的多种自身免疫性疾病的发病机制中也起着重要作用，越来越多的证据表明Th 17细胞上的CCR 2可能成为MS的治疗靶点。
Multiple sclerosis (MS) is a CD4+ T cell-mediated autoimmune disease affecting the central nervous system. It was largely accepted that Th1 cells driven by IL-12 were pathogenic T cells in human MS and experimental autoimmune encephalomyelitis, an animal model of MS. Recent data have established that IL-17-producing CD4+ T cells, driven by IL-23 and referred to as Th17 cells, play a pivotal role in the pathogenesis of EAE. A combination of TGF-beta and IL-6 induce Th17 cell lineage commitment via expression of transcription factor RORgammat. Th17 cells and induced Foxp3+ T regulatory cells are in reciprocal position in the T cell lineage commitment governed by TGF-beta and IL-6. The vitamin A metabolite retinoic acid is involved in this process via TGF-beta dependent induction of Foxp3. We have demonstrated that human Th17 cells could be identified as CCR2+ CCR5- memory CD4+ T cells. It is becoming clear that IL-23/Th17 axis also plays an important role in the pathogenesis of various human autoimmune diseases including MS. Additionally, accumulating evidences raise a possibility that CCR2 on Th17 cells may be a therapeutic target in MS.