Kobayashi Takashi, Walsh Patrick T, Walsh Matthew C, Speirs Kendra M, Chiffoleau Elise, King Carolyn G, Hancock Wayne W, Caamano Jorge H, Hunter Christopher A, Scott Phillip, Turka Laurence A, Choi Yongwon
Abramson Family Cancer Research Institute, Philadelphia, PA 19104, USA.
Immunity. 2003 Sep;19(3):353-63. doi: 10.1016/s1074-7613(03)00230-9.
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.
白细胞介素-1受体（IL-1R）/Toll样受体（TLR）家族以及肿瘤坏死因子受体（TNFR）超家族成员对于调节树突状细胞（DC）生物学的多个方面至关重要。与每个家族相关的几种信号通路利用衔接分子TRAF6，但它在DC中的作用尚不清楚。通过研究TRAF6缺陷小鼠以及用TRAF6缺陷胎儿肝细胞重建的骨髓（BM）嵌合体，我们发现适当的DC成熟需要TRAF6。响应微生物成分或CD40L时，TRAF6缺陷的DC无法上调MHCII和B7.2的表面表达，也无法产生炎性细胞因子。此外，经脂多糖（LPS）处理的TRAF6缺陷DC没有表现出增强的刺激初始T细胞的能力。有趣的是，在TRAF6缺陷小鼠和BM嵌合体中，脾DC的主要群体，即CD4(+)CD8alpha(-)亚群几乎不存在。这些结果共同表明，TRAF6调节DC成熟、激活和发育所需的关键过程，DC是先天性免疫和适应性免疫之间的主要细胞桥梁。
