TRAF6 is a critical factor for dendritic cell maturation and development
TRAF6 is a critical factor for dendritic cell maturation and development
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DOI：
10.1016/s1074-7613(03)00230-9
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发表时间：
2003-09-01
期刊：
影响因子：
32.4
通讯作者：
Choi, YW
中科院分区：
文献类型：
--
作者：
Kobayashi, T;Walsh, PT;Choi, YW
IL-1受体(IL-1R)/ toll样受体（TLR）家族和TNF受体（TNFR）超家族成员对调节树突状细胞（DC）生物学的多个方面至关重要。与每个家族相关的几个信号通路利用适配器分子TRAF6，但其在dc中的作用尚不清楚。通过检测TRAF6缺陷小鼠和用TRAF6缺陷胎儿肝细胞重建的骨髓嵌合体，我们发现DC的正常成熟需要TRAF6。在对微生物成分或CD40L的反应中，traf6缺陷dc不能上调MHCII和B7.2的表面表达，也不能产生炎症细胞因子。此外，lps处理的traf6缺陷dc并没有表现出增强的刺激幼稚T细胞的能力。有趣的是，脾dc的一个主要群体，CD4(+)CD8alpha（-）亚群，在traf6缺陷小鼠和BM嵌合体中几乎不存在。综上所述，这些结果表明TRAF6调节了dc成熟、激活和发育所需的关键过程，dc是先天免疫和适应性免疫之间的主要细胞桥梁。
IL-1 receptor (IL-1R)/Toll-like receptor (TLR) family and TNF receptor (TNFR) superfamily members are critical for regulating multiple aspects of dendritic cell (DC) biology. Several signaling pathways associated with each family utilize the adapter molecule, TRAF6, but its role in DCs is unclear. By examining TRAF6-deficient mice and bone marrow (BM) chimeras reconstituted with TRAF6-deficient fetal liver cells, we show that proper DC maturation requires TRAF6. In response to either microbial components or CD40L, TRAF6-deficient DCs fail to upregulate surface expression of MHCII and B7.2, or produce inflammatory cytokines. Moreover, LPS-treated TRAF6-deficient DCs do not exhibit an enhanced capacity to stimulate naive T cells. Interestingly, a major population of splenic DCs, the CD4(+)CD8alpha(-) subset, is nearly absent in both TRAF6-deficient mice and BM chimeras. Together these results indicate that TRAF6 regulates the critical processes required for maturation, activation, and development of DCs, the primary cellular bridge between innate and adaptive immunity.