The keratin-related Ouroboros proteins function as immune antigens mediating tail regression in Xenopus metamorphosis
The keratin-related Ouroboros proteins function as immune antigens mediating tail regression in Xenopus metamorphosis
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DOI：
10.1073/pnas.0708837106
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发表时间：
2009-10-27
影响因子：
11.1
通讯作者：
Izutsu, Yumi
中科院分区：
文献类型：
--
作者：
Mukaigasa, Katsuki;Hanasaki, Akira;Izutsu, Yumi
在两栖动物的变形过程中，尾巴的吸收被认为主要是由甲状腺激素触发的细胞程序性死亡的细胞自主机制控制的。然而，我们已经提出了免疫反应在变态中的作用，基于同种蝌蚪尾皮肤移植到成年非洲爪蟾动物体内会被T细胞排斥。为了验证这一点，我们鉴定了两个尾部抗原基因，称为ouro1和ouro2，它们编码角蛋白相关蛋白。重组Ouro1和Ouro2蛋白在体外分离的成年爪蟾T细胞中产生增殖反应。这些基因在尾皮中特异表达于变态高潮。当ouro1和ouro2在尾区过表达时，可诱导成人型T细胞完全分化后的T细胞聚集和尾部过早变性。当敲低ouro1和ouro2的表达时，即使在变态完成后，尾皮组织仍然存在。我们的研究结果表明，Ouro蛋白作为免疫抗原参与了尾巴退化的过程，并强调了获得性免疫系统不仅有助于自卫，还有助于脊椎动物形态发生的重塑过程的可能性。
Tail resorption during amphibian metamorphosis has been thought to be controlled mainly by a cell-autonomous mechanism of programmed cell death triggered by thyroid hormone. However, we have proposed a role for the immune response in metamorphosis, based on the finding that syngeneic grafts of tadpole tail skin into adult Xenopus animals are rejected by T cells. To test this, we identified two tail antigen genes called ouro1 and ouro2 that encode keratin-related proteins. Recombinant Ouro1 and Ouro2 proteins generated proliferative responses in vitro in T cells isolated from naive adult Xenopus animals. These genes were expressed specifically in the tail skin at the climax of metamorphosis. Overexpression of ouro1 and ouro2 induced T-cell accumulation and precocious tail degeneration after full differentiation of adult-type T cells when overexpressed in the tail region. When the expression of ouro1 and ouro2 were knocked down, tail skin tissue remained even after metamorphosis was complete. Our findings indicate that Ouro proteins participate in the process of tail regression as immune antigens and highlight the possibility that the acquired immune system contributes not only to self-defense but also to remodeling processes in vertebrate morphogenesis.