Touil Tarik, Fitzgerald Denise, Zhang Guang-Xian, Rostami A M, Gran Bruno
Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Drug News Perspect. 2006 Mar;19(2):77-83. doi: 10.1358/dnp.2006.19.2.977443.
Interleukin-23 (IL-23) is a heterodimeric cytokine that is composed of a p40 subunit, shared with the closely related cytokine IL-12, and a smaller IL-23p19 subunit. It belongs to a family of heterodimeric cytokines that also includes IL-12 and IL-27. Experimental autoimmune encephalomyelitis (EAE) is an autoimmune disease that serves as a model for multiple sclerosis, an inflammatory demyelinating disease of the central nervous system that is a frequent cause of disability in young adults. EAE is thought to be initiated by CD4+ T cells. The production of interferon-gamma and tumor necrosis factor-alpha (T helper 1 [Th1] phenotype) was considered a marker for the ability of such cells to induce disease. Consistent with this view, IL-12, a cytokine that induces the differentiation of Th1 cells, was considered essential for EAE susceptibility. However, it is now clear that IL-23 rather than IL-12 is required for EAE susceptibility. IL-23 induces a population of IL-17-producing cells that is more critically involved in EAE pathogenesis than Th1 cells. Here, we review the role of the IL-23 system in the pathophysiology of EAE.
白细胞介素-23（IL-23）是一种异二聚体细胞因子，由一个与密切相关的细胞因子IL-12共享的p40亚基和一个较小的IL-23p19亚基组成。它属于一个异二聚体细胞因子家族，该家族还包括IL-12和IL-27。实验性自身免疫性脑脊髓炎（EAE）是一种自身免疫性疾病，可作为多发性硬化症的模型，多发性硬化症是一种中枢神经系统的炎性脱髓鞘疾病，是年轻成年人致残的常见原因。EAE被认为是由CD4 + T细胞引发的。干扰素-γ和肿瘤坏死因子-α（辅助性T细胞1 [Th1]表型）的产生被认为是此类细胞诱导疾病能力的标志物。与这一观点一致，IL-12是一种诱导Th1细胞分化的细胞因子，被认为对EAE易感性至关重要。然而，现在很清楚，EAE易感性需要的是IL-23而不是IL-12。IL-23诱导一群产生IL-17的细胞，这群细胞比Th1细胞更关键地参与EAE发病机制。在这里，我们综述了IL-23系统在EAE病理生理学中的作用。
