Yoshida Hiroki
Department of Biomolecular Sciences, Faculty of Medicine, Saga University.
Nihon Rinsho Meneki Gakkai Kaishi. 2009 Aug;32(4):202-13. doi: 10.2177/jsci.32.202.
Cytokine-mediated immunity plays a crucial role in the pathogenesis of various diseases including autoimmunity. Recently, IL-27 was identified, which along with IL-12, 23 and 35 belongs to the IL-12 cytokine family. These family members play roles in regulation of Th cell differentiation. IL-27 is unique in that while it induces Th1 differentiation, the same cytokine suppresses immune responses. In the absence of IL-27-mediated immunosuppression, hyper-production of various pro-inflammatory cytokines concomitant with severe inflammation in affected organs was observed in IL-27 receptor alpha chain (WSX-1)-deficient mice infected with Trypanosoma cruzi. Experimental allergic or inflammatory responses were also enhanced in WSX-1-deficient mice. The immunosuppressive effects of IL-27 depend on inhibition of the development of Th 17 cells (a newly identified inflammatory T helper population), and induction of IL-10 production. Moreover, administration of IL-27 or augmentation of IL-27 signaling suppresses some diseases of autoimmune or allergic origin, including encephalitis, arthritis, and systemic lupus erythematosus, demonstrating its potential in therapy of diseases mediated by inflammatory cytokines.
细胞因子介导的免疫在包括自身免疫性疾病在内的多种疾病的发病机制中起着关键作用。最近，白细胞介素-27（IL-27）被发现，它与IL-12、IL-23和IL-35同属IL-12细胞因子家族。这些家族成员在调节辅助性T细胞（Th）分化中发挥作用。IL-27的独特之处在于，它既能诱导Th1分化，又能抑制免疫反应。在感染克氏锥虫的IL-27受体α链（WSX-1）缺陷小鼠中，在没有IL-27介导的免疫抑制的情况下，观察到各种促炎细胞因子过度产生，同时受影响器官出现严重炎症。在WSX-1缺陷小鼠中，实验性过敏或炎症反应也增强。IL-27的免疫抑制作用取决于对Th17细胞（一种新发现的炎症性辅助性T细胞群体）发育的抑制以及IL-10产生的诱导。此外，给予IL-27或增强IL-27信号传导可抑制一些自身免疫性或过敏性疾病，包括脑炎、关节炎和系统性红斑狼疮，证明了其在治疗炎症细胞因子介导的疾病方面的潜力。
