title: Fibroblastic reticular cell-derived lysophosphatidic acid regulates confined intranodal T-cell motility.
abstract: Lymph nodes (LNs) are highly confined environments with a cell-dense three-dimensional meshwork, in which lymphocyte migration is regulated by intracellular contractile proteins. However, the molecular cues directing intranodal cell migration remain poorly characterized. Here we demonstrate that lysophosphatidic acid (LPA) produced by LN fibroblastic reticular cells (FRCs) acts locally to LPA2 to induce T-cell motility. In vivo, either specific ablation of LPA-producing ectoenzyme autotaxin in FRCs or LPA2 deficiency in T cells markedly decreased intranodal T cell motility, and FRC-derived LPA critically affected the LPA2-dependent T-cell motility. In vitro, LPA activated the small GTPase RhoA in T cells and limited T-cell adhesion to the underlying substrate via LPA2. The LPA-LPA2 axis also enhanced T-cell migration through narrow pores in a three-dimensional environment, in a ROCK-myosin II-dependent manner. These results strongly suggest that FRC-derived LPA serves as a cell-extrinsic factor that optimizes T-cell movement through the densely packed LN reticular network.
authors.affiliation: Laboratory of Immunodynamics, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Osaka, Japan.|WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.|MediCity Research Laboratory, University of Turku, Turku, Finland.
authors.forename: Akira
authors.initials: A
authors.lastname: Takeda
authors.affiliation: Laboratory of Immunodynamics, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Osaka, Japan.|WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.
authors.forename: Daichi
authors.initials: D
authors.lastname: Kobayashi
authors.affiliation: WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.|Department of Immunology and Cell Biology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Aoi
authors.affiliation: Laboratory of Immunodynamics, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Sasaki
authors.affiliation: Department of Biochemistry, Keio University School of Medicine, Tokyo, Japan.|JST Precursory Research for Embryonic Science and Technology project, Saitama, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Sugiura
authors.affiliation: Department of Immunology, Graduate School of Medicine, Akita University, Akita, Japan.
authors.forename: Hidemitsu
authors.initials: H
authors.lastname: Igarashi
authors.affiliation: Department of Anatomy, Kansai University of Health Sciences, Awaji, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tohya
authors.affiliation: Laboratory of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: Asuka
authors.initials: A
authors.lastname: Inoue
authors.affiliation: Laboratory of Immunodynamics, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Osaka, Japan.|WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.
authors.forename: Erina
authors.initials: E
authors.lastname: Hata
authors.affiliation: Department of Immunology, Graduate School of Medicine, Akita University, Akita, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Akahoshi
authors.affiliation: Laboratory of Immunodynamics, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Osaka, Japan.|WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.
authors.forename: Haruko
authors.initials: H
authors.lastname: Hayasaka
authors.affiliation: WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.|Department of Immunology and Cell Biology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Kikuta
authors.affiliation: Institute of Immunobiology, Kantonal Hospital St. Gallen, St. Gallen, Switzerland.
authors.forename: Elke
authors.initials: E
authors.lastname: Scandella
authors.affiliation: Institute of Immunobiology, Kantonal Hospital St. Gallen, St. Gallen, Switzerland.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Ludewig
authors.affiliation: Department of Immunology, Graduate School of Medicine, Akita University, Akita, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ishii
authors.affiliation: Laboratory of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: Junken
authors.initials: J
authors.lastname: Aoki
authors.affiliation: Department of Biochemistry, Keio University School of Medicine, Tokyo, Japan.|Core Research for Evolutional Science and Technology project, Saitama, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Suematsu
authors.affiliation: WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.|Department of Immunology and Cell Biology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Ishii
authors.affiliation: WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.|Laboratory of Immune Regulation, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takeda
authors.affiliation: MediCity Research Laboratory, University of Turku, Turku, Finland.
authors.forename: Sirpa
authors.initials: S
authors.lastname: Jalkanen
authors.affiliation: Laboratory of Immunodynamics, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Osaka, Japan.|WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.|MediCity Research Laboratory, University of Turku, Turku, Finland.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Miyasaka
authors.affiliation: Laboratory of Immunodynamics, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Osaka, Japan.|WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Umemoto
mesh_terms: D000818:Animals; D002465:Cell Movement; D005347:Fibroblasts / Q000378:metabolism*; D008246:Lysophospholipids / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D008246:Lysophospholipids; D020742:rhoA GTP-Binding Protein; C032881:lysophosphatidic acid
keywords: Fibroblastic reticular cell; Lymph node; Lymphocyte migration; Lysophospholipid; cell biology; immunology; mouse
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