IL-12-polarized Th1 cells produce GM-CSF and induce EAE independent of IL-23.
IL-12-polarized Th1 cells produce GM-CSF and induce EAE independent of IL-23.
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DOI：
10.1002/eji.201545800
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发表时间：
2015-10
影响因子：
5.4
通讯作者：
Segal BM
中科院分区：
文献类型：
--
作者：
Grifka-Walk HM;Giles DA;Segal BM
针对髓鞘抗原的反应性CD 4 + T辅助（Th）细胞介导动物模型实验性自身免疫性脑脊髓炎（EAE），并且已经涉及多发性硬化（MS）的发病机制。它是目前争论是否致脑炎Th细胞是异质性或来自单一的谱系。在目前的研究中，我们挑战了这样一个教条，即髓磷脂反应性T细胞获得致病特性普遍需要单核因子IL-23的刺激。我们发现IL-12调节的Th 1细胞在中枢神经系统（CNS）中容易产生IFN-γ和GM-CSF，并通过IL-23非依赖性途径诱导严重形式的EAE。Th 1介导的EAE以富含单核细胞的CNS浸润为特征，在CNS中引起强烈的促炎细胞因子应答，并且部分依赖于CCR 2。相反，IL-23调节的稳定的Th 17细胞通过IL-12非依赖性途径诱导EAE，其过程相对温和。这些数据提供了明确的证据，表明自身免疫性疾病可以由不同的CD 4 + T辅助细胞亚群和极化因子驱动。
CD4+ T-helper (Th) cells reactive against myelin antigens mediate the animal model experimental autoimmune encephalomyelitis (EAE) and have been implicated in the pathogenesis of multiple sclerosis (MS). It is currently debated whether encephalitogenic Th cells are heterogeneous or arise from a single lineage. In the current study, we challenge the dogma that stimulation with the monokine IL-23 is universally required for the acquisition of pathogenic properties by myelin-reactive T cells. We show that IL-12-modulated Th1 cells readily produce IFN-γ and GM-CSF in the central nervous system (CNS) and induce a severe form of EAE via an IL-23-independent pathway. Th1-mediated EAE is characterized by monocyte-rich CNS infiltrates, elicits a strong proinflammatory cytokine response in the CNS, and is partially CCR2-dependent. Conversely, IL-23-modulated, stable Th17 cells induce EAE with a relatively mild course via an IL-12-independent pathway. These data provide definitive evidence that autoimmune disease can be driven by distinct CD4+ T helper cell subsets and polarizing factors.