DAP12-deficient mice fail to develop autoimmunity due to impaired antigen priming
DAP12-deficient mice fail to develop autoimmunity due to impaired antigen priming
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DOI：
10.1016/s1074-7613(00)00034-0
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发表时间：
2000-09-01
期刊：
影响因子：
32.4
通讯作者：
Lanier, LL
中科院分区：
文献类型：
--
作者：
Bakker, ABH;Hoek, RM;Lanier, LL
DAP12 是一种带有 ITAM 的膜接头分子，与 NK 和骨髓细胞的激活有关。在因靶向基因破坏而导致 DAP12 缺陷的小鼠中，尽管 NK 细胞上的激活 Ly49 受体下调且无功能，但淋巴和骨髓发育明显正常。为了分析体内 DAP12 缺乏的后果，我们检测了 DAP12(-/-) 小鼠对实验性自身免疫性脑脊髓炎 (EAE) 的易感性。 DAP12-/- 小鼠对髓鞘少突胶质细胞糖蛋白 (MOG) 肽免疫诱导的 EAE 具有抵抗力。由于体内 T 细胞启动不足，耐药性与髓磷脂反应性 CD4(+) T 细胞产生 IFN γ 的强烈减少有关。这些数据表明 DAP12 信号传导可能是最佳抗原呈递细胞 (APC) 功能或炎症所必需的。
DAP12 is an ITAM-bearing membrane adaptor molecule implicated in the activation of NK and myeloid cells. In mice rendered DAP12 deficient by targeted gene disruption, lymphoid and myeloid development was apparently normal, although the activating Ly49 receptors on NK cells were downregulated and nonfunctional. To analyze the consequences of DAP12 deficiency in vivo, we examined the susceptibility of DAP12(-/-) mice to experimental autoimmune encephalomyelitis (EAE). DAP12-/- mice were resistant to EAE induced by immunization with myelin oligodendrocyte glycoprotein (MOG) peptide. Resistance was associated with a strongly diminished production of IFN gamma by myelin-reactive CD4(+) T cells due to inadequate T cell priming in vivo. These data suggest that DAP12 signaling may be required for optimal antigen-presenting cell (APC) function or inflammation.