title: Chemokine-dependent T cell migration requires aquaporin-3-mediated hydrogen peroxide uptake.
abstract: 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 (H(2)O(2)) uptake but not the canonical water/glycerol transport. AQP3-mediated H(2)O(2) 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 H(2)O(2) uptake is required for chemokine-dependent T cell migration in sufficient immune response.
authors.affiliation: Department of Dermatology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. haramari@kuhp.kyoto-u.ac.jp
authors.forename: Mariko
authors.initials: M
authors.lastname: Hara-Chikuma
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Chikuma
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Sugiyama
authors.forename: Kenji
authors.initials: K
authors.lastname: Kabashima
authors.forename: Alan S
authors.initials: AS
authors.lastname: Verkman
authors.forename: Shintaro
authors.initials: S
authors.lastname: Inoue
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Miyachi
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D051400:Aquaporin 3 / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport; D002465:Cell Movement / Q000276:immunology*; D054377:Chemokine CXCL12 / Q000276:immunology; D018925:Chemokines / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D005786:Gene Expression Regulation; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010539:Permeability; D055503:Protein Multimerization / Q000276:immunology; D015398:Signal Transduction; D012867:Skin / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D014867:Water / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism
chemical_list: D000199:Actins; C496028:Aqp3 protein, mouse; D054377:Chemokine CXCL12; D018925:Chemokines; D014867:Water; D051400:Aquaporin 3; D006861:Hydrogen Peroxide; D020764:cdc42 GTP-Binding Protein