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

Chemokine-dependent trafficking is indispensable for the effector function of antigenexperienced 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.