TRAF6 is a T cell-intrinsic negative regulator required for the maintenance of immune homeostasis
TRAF6 is a T cell-intrinsic negative regulator required for the maintenance of immune homeostasis
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DOI：
10.1038/nm1449
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发表时间：
2006-09-01
期刊：
影响因子：
82.9
通讯作者：
Choi, Yongwon
中科院分区：
文献类型：
--
作者：
King, Carolyn G.;Kobayashi, Takashi;Choi, Yongwon
TRAF 6通过介导来自TNF受体和白细胞介素-1受体/Toll样受体超家族的信号在先天免疫应答的调节中具有关键作用。在这里，我们发现T细胞特异性TRAF 6缺失意外地导致多器官炎症性疾病。与野生型T细胞相比，TRAF 6缺陷型T细胞表现出磷脂酰肌醇3-激酶（PI 3 K）-Akt通路的过度活化，因此，对CD 4（+）CD 25（+）调节性T细胞的抑制具有抗性。这些数据鉴定了TRAF 6在维持外周耐受性中的先前未被认识的作用，并表明存在T细胞内在控制机制以使应答T细胞对耐受性信号敏感。
TRAF6 has a key role in the regulation of innate immune responses by mediating signals from both TNF receptor and interleukin-1 receptor/Toll-like receptor superfamilies. Here we show that T cell - specific deletion of TRAF6 unexpectedly results in multiorgan inflammatory disease. TRAF6-deficient T cells exhibit hyperactivation of the phosphatidylinositol 3-kinase (PI3K)-Akt pathway compared with wild-type T cells and, as a result, become resistant to suppression by CD4(+)CD25(+) regulatory T cells. These data identify a previously unrecognized role for TRAF6 in the maintenance of peripheral tolerance, and suggest the presence of a T cell - intrinsic control mechanism to render responder T cells susceptible to tolerizing signals.