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

2012; Rockefeller University Press; Volume: 209; Issue: 10 Linguagem: Inglês

10.1084/jem.20112398

1540-9538

Mariko Hara‐Chikuma, Shunsuke Chikuma, Yoshinori Sugiyama, Kenji Kabashima, A. S. Verkman, Shintaro Inoue, Yoshiki Miyachi,

T-cell and B-cell Immunology

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.