TNF receptor-associated factor 5 limits the induction of Th2 immune responses
TNF receptor-associated factor 5 limits the induction of Th2 immune responses
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DOI：
10.4049/jimmunol.172.7.4292
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发表时间：
2004-04-01
影响因子：
4.4
通讯作者：
Croft, M
中科院分区：
文献类型：
--
作者：
So, T;Salek-Ardakani, S;Croft, M
TNF受体相关因子（TRAF）分子家族作为由TNF受体（TNFR）超家族的几个成员启动的信号传导途径的衔接蛋白。TRAF 5-/-动物是可行的，尽管与几个TNFR家族成员相互作用，但免疫系统发育正常。TRAF 5的明确作用尚未显现。OX 40（CD 134）与TRAF 5相互作用，表明该途径可能参与调节T细胞分化为Th 1或Th 2细胞。在组织培养中，TRAF 5（-/-）T细胞的OX 40刺激导致显著的Th 2表型，IL-4和IL-5水平升高。类似地，在存在激动剂抗0X 40 Ab的情况下用佐剂中的蛋白质进行体内免疫导致TRAF 5（-/-）小鼠中Th 2发育增强。此外，由T细胞诱导的肺部炎症（由OX 40严格控制）在TRAF 5（-/-）小鼠中更为明显，其特征在于Th 2细胞因子水平较高。这些结果表明TRAF 5可以限制Th 2应答的诱导，并且TRAF 5可以在调节由OX 40共刺激驱动的应答中发挥作用。
The TNF receptor-associated factor (TRAF) family of molecules acts as adapter proteins for signaling pathways initiated by several members of the TNF receptor (TNFR) superfamily. TRAF5-/- animals are viable and have normal development of the immune system despite interacting with several TNFR family members. A clear role for TRAF5 has yet to emerge. OX40 (CD134) interacts with TRAF5, suggesting that this pathway could be involved in regulating T cell differentiation into Th1 or Th2 cells. In tissue culture, OX40 stimulation of TRAF5(-/-) T cells resulted in a pronounced Th2 phenotype with elevated levels of IL-4 and IL-5. Similarly, in vivo immunization with protein in adjuvant in the presence of an agonist anti-OX40 Ab resulted in enhanced Th2 development in TRAF5(-/-) mice. Additionally, lung inflammation induced by T cells, which is critically controlled by OX40, was more pronounced in TRAF5(-/-) mice, characterized by higher levels of Th2 cytokines. These results suggest that TRAF5 can limit the induction of Th2 responses, and that TRAF5 can play a role in modulating responses driven by OX40 costimulation.