IL-27 suppresses Th2 cell development and Th2 cytokines production from polarized Th2 cells: A novel therapeutic way for Th2-mediated allergic inflammation
IL-27 suppresses Th2 cell development and Th2 cytokines production from polarized Th2 cells: A novel therapeutic way for Th2-mediated allergic inflammation
复制标题
DOI：
10.4049/jimmunol.179.7.4415
复制
发表时间：
2007-10-01
影响因子：
4.4
通讯作者：
Nakanishi, Kenji
中科院分区：
文献类型：
--
作者：
Yoshimoto, Tomohiro;Yoshimoto, Takayuki;Nakanishi, Kenji
IL-27上调Th 1但下调Th 2应答。但其分子机制及对极化Th 2细胞的调节作用尚不清楚。在这项研究中，我们已经发现，IL-27抑制Th 2细胞的发展，以及Th 2细胞因子的生产已经极化的Th 2细胞通过下调加塔-3和上调T-bet表达的同时。在体内每天IL-27治疗1周后，利什曼原虫感染保护BALB/c小鼠足垫肿胀减少寄生虫负荷通过相互调节Th 1和Th 2反应。此外，IL-27刺激导致宿主小鼠对委内瑞拉圆线虫感染产生Th 2应答的能力显著降低。因此，IL-27处理的小鼠在S.委内瑞拉感染，并表现出显着延迟寄生虫驱逐。最后，鼻内给予IL-27抑制OVA致敏动物中OVA诱导的气道高反应性和炎症。因此，IL-27可能为支气管哮喘等Th 2相关疾病的治疗提供新的途径。
IL-27 up-regulates Th1 but down-regulates Th2 responses. However, its molecular mechanism and regulatory effects on polarized Th2 cells remain unclear. In this study, we have revealed that IL-27 inhibits Th2 cell development as well as Th2 cytokines production from already polarized Th2 cells by down-regulation of GATA-3 and up-regulation of T-bet expression simultaneously. In vivo daily IL-27 treatment for 1 wk after Leishmania major infection protects BALB/c mice from footpad swelling by diminishing parasite burden via reciprocal regulation of Th1 and Th2 responses. Furthermore, IL-27 stimulation causes marked reduction in the capacity of host mouse to mount a Th2 response against Strongyloides venezuelensis infection. Thus, IL-27-treated mice failed to develop intestinal mastocytosis after S. venezuelensis infection and exhibited a marked delay in parasite expulsion. Finally, intranasal administration of IL-27 inhibits OVA-induced airway hyperresponsiveness and inflammation in OVA-sensitized animals. Thus, IL-27 could provide us with a novel therapeutic way for treating Th2-associated diseases such as bronchial asthma.