So Takanori, Salek-Ardakani Shahram, Nakano Hiroyasu, Ware Carl F, Croft Michael
Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA.
J Immunol. 2004 Apr 1;172(7):4292-7. doi: 10.4049/jimmunol.172.7.4292.
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.
肿瘤坏死因子受体相关因子（TRAF）家族分子作为衔接蛋白，参与由肿瘤坏死因子受体（TNFR）超家族的多个成员启动的信号通路。尽管TRAF5（-/-）动物与多个TNFR家族成员相互作用，但其仍具有活力且免疫系统发育正常。TRAF5的明确作用尚未显现。OX40（CD134）与TRAF5相互作用，提示该信号通路可能参与调节T细胞分化为Th1或Th2细胞。在组织培养中，用OX40刺激TRAF5（-/-）T细胞会导致明显的Th2表型，白细胞介素-4（IL-4）和白细胞介素-5（IL-5）水平升高。同样，在存在激动剂抗OX40抗体的情况下，用佐剂中的蛋白质进行体内免疫会导致TRAF5（-/-）小鼠的Th2发育增强。此外，由T细胞诱导的肺部炎症（由OX40严格控制）在TRAF5（-/-）小鼠中更为明显，其特征是Th2细胞因子水平更高。这些结果表明，TRAF5可以限制Th2反应的诱导，并且TRAF5可以在调节由OX40共刺激驱动的反应中发挥作用。
