Chemokine-dependent T cell migration requires aquaporin-3-mediated hydrogen peroxide uptake.

Chemokine-dependent T cell migration requires aquaporin-3-mediated hydrogen peroxide uptake.
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DOI:
10.1084/jem.20112398
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发表时间:
2012-09-24
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Miyachi Y
Miyachi Y
中科院分区:
其他
文献类型:
--
作者:
Hara-Chikuma M;Chikuma S;Sugiyama Y;Kabashima K;Verkman AS;Inoue S;Miyachi Y

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在免疫反应中,水/甘油通道水通道蛋白-3是依赖趋化因子的T细胞迁移所必需的。在免疫应答过程中,依赖于趋化因子的运输对于经历抗原的T细胞的效应器功能是不可或缺的。在这项研究中,我们报道了水/甘油通道水通道水通道蛋白-3(AQP3)在T细胞上的表达,并调节它们在皮肤免疫反应中的运输。T细胞向趋化因子的迁移依赖于AQP3介导的过氧化氢(H_2O_2)摄取,而不是典型的水/甘油转运。AQP3介导的H_2O_2转运对于Rho家族GTP酶CDc42的激活和随后的肌动蛋白动力学是必不可少的。巧合的是,AQP3缺陷小鼠在半抗原诱导的接触性超敏反应方面存在缺陷,这归因于抗原启动的T细胞向半抗原攻击皮肤的运输受损。因此,我们认为AQP3介导的过氧化氢摄取是依赖趋化因子的T细胞在充分的免疫反应中迁移所必需的。
The water/glycerol channel aquaporin-3 is required for chemokine-dependent T cell migration during immune responses. Chemokine-dependent trafficking is indispensable for the effector function of antigen-experienced T cells during immune responses. In this study, we report that the water/glycerol channel aquaporin-3 (AQP3) is expressed on T cells and regulates their trafficking in cutaneous immune reactions. T cell migration toward chemokines is dependent on AQP3-mediated hydrogen peroxide (H2O2) uptake but not the canonical water/glycerol transport. AQP3-mediated H2O2 transport is essential for the activation of the Rho family GTPase Cdc42 and the subsequent actin dynamics. Coincidentally, AQP3-deficient mice are defective in the development of hapten-induced contact hypersensitivity, which is attributed to the impaired trafficking of antigen-primed T cells to the hapten-challenged skin. We therefore suggest that AQP3-mediated H2O2 uptake is required for chemokine-dependent T cell migration in sufficient immune response.
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