title: Resolvin E1 inhibits dendritic cell migration in the skin and attenuates contact hypersensitivity responses.
abstract: Resolvin E1 (RvE1) is a lipid mediator derived from ω3 polyunsaturated fatty acids that exerts potent antiinflammatory roles in several murine models. The antiinflammatory mechanism of RvE1 in acquired immune responses has been attributed to attenuation of cytokine production by dendritic cells (DCs). In this study, we newly investigated the effect of RvE1 on DC motility using two-photon microscopy in a contact hypersensitivity (CHS) model and found that RvE1 impaired DC motility in the skin. In addition, RvE1 attenuated T cell priming in the draining lymph nodes and effector T cell activation in the skin, which led to the reduced skin inflammation in CHS. In contrast, leukotriene B4 (LTB4) induced actin filament reorganization in DCs and increased DC motility by activating Cdc42 and Rac1 via BLT1, which was abrogated by RvE1. Collectively, our results suggest that RvE1 attenuates cutaneous acquired immune responses by inhibiting cutaneous DC motility, possibly through LTB4-BLT1 signaling blockade.
authors.affiliation: Department of Dermatology and Center for Innovation in Immunoregulative Technology and Therapeutics, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8501, Japan Department of Dermatology, University of Occupational and Environmental Health, Kitakyushu, Fukuoka 807-8555, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sawada
authors.affiliation: Department of Dermatology and Center for Innovation in Immunoregulative Technology and Therapeutics, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8501, Japan Department of Dermatology and Center for Innovation in Immunoregulative Technology and Therapeutics, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8501, Japan hontetsu@kuhp.kyoto-u.ac.jp kaba@kuhp.kyoto-u.ac.jp.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Honda
authors.affiliation: Department of Dermatology and Center for Innovation in Immunoregulative Technology and Therapeutics, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Hanakawa
authors.affiliation: Department of Dermatology and Center for Innovation in Immunoregulative Technology and Therapeutics, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nakamizo
authors.affiliation: Department of Dermatology and Center for Innovation in Immunoregulative Technology and Therapeutics, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Teruasa
authors.initials: T
authors.lastname: Murata
authors.affiliation: Department of Dermatology and Center for Innovation in Immunoregulative Technology and Therapeutics, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Ueharaguchi-Tanada
authors.affiliation: Department of Dermatology and Center for Innovation in Immunoregulative Technology and Therapeutics, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Ono
authors.affiliation: Department of Dermatology and Center for Innovation in Immunoregulative Technology and Therapeutics, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Amano
authors.affiliation: Department of Dermatology and Center for Innovation in Immunoregulative Technology and Therapeutics, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Saeko
authors.initials: S
authors.lastname: Nakajima
authors.affiliation: Department of Dermatology and Center for Innovation in Immunoregulative Technology and Therapeutics, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Gyohei
authors.initials: G
authors.lastname: Egawa
authors.affiliation: Department of Dermatology and Center for Innovation in Immunoregulative Technology and Therapeutics, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Tanizaki
authors.affiliation: Department of Dermatology and Center for Innovation in Immunoregulative Technology and Therapeutics, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Otsuka
authors.affiliation: Department of Dermatology and Center for Innovation in Immunoregulative Technology and Therapeutics, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kitoh
authors.affiliation: Department of Dermatology and Center for Innovation in Immunoregulative Technology and Therapeutics, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Teruki
authors.initials: T
authors.lastname: Dainichi
authors.affiliation: Department of Biomolecular Engineering, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Meguro-ku, Tokyo 152-8550, Japan.
authors.forename: Narihito
authors.initials: N
authors.lastname: Ogawa
authors.affiliation: Department of Biomolecular Engineering, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Meguro-ku, Tokyo 152-8550, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Department of Biochemistry, Juntendo University School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Yokomizo
authors.affiliation: PRESTO, Japan Science and Technology Agency, Chiyoda-ku, Tokyo 102-0076, Japan Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan Graduate School of Medical Life Science, Yokohama City University, Kanazawa-ku, Yokohama 236-0027, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Arita
authors.affiliation: Department of Dermatology, University of Occupational and Environmental Health, Kitakyushu, Fukuoka 807-8555, Japan.
authors.forename: Motonobu
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Dermatology and Center for Innovation in Immunoregulative Technology and Therapeutics, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Miyachi
authors.affiliation: Department of Dermatology and Center for Innovation in Immunoregulative Technology and Therapeutics, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8501, Japan PRESTO, Japan Science and Technology Agency, Chiyoda-ku, Tokyo 102-0076, Japan hontetsu@kuhp.kyoto-u.ac.jp kaba@kuhp.kyoto-u.ac.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kabashima
mesh_terms: D000199:Actins / Q000737:chemistry; D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000502:physiology; D003877:Dermatitis, Contact / Q000188:drug therapy*; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D007975:Leukotriene B4 / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018102:Receptors, Leukotriene B4 / Q000502:physiology; D012867:Skin / Q000276:immunology*
chemical_list: D000199:Actins; C503704:Ltb4r1 protein, mouse; D018102:Receptors, Leukotriene B4; D007975:Leukotriene B4; D007371:Interferon-gamma; D015118:Eicosapentaenoic Acid; C499823:5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid