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Role of SLURP-1, an endogenous alpha7 nicotinic acetylcholine receptor allosteric ligand, in T cell differentiation

Research Project

Project/Area Number 15K07969
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pharmacology in pharmacy
Research InstitutionKitasato University

Principal Investigator

Kawashima Koichiro  北里大学, 薬学部, 客員教授 (70095008)

Co-Investigator(Kenkyū-buntansha) 藤井 健志  同志社女子大学, 薬学部, 教授 (80255380)
間下 雅士  同志社女子大学, 薬学部, 助教 (30738886)
堀口 和秀  福井大学, 学術研究院医学系部門, 准教授 (20377451)
Co-Investigator(Renkei-kenkyūsha) MISAWA Hidemi  慶応大学, 薬学部, 教授 (80219617)
MORIWAKI Yasuhiro  慶応大学, 薬学部, 講師 (00392150)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
KeywordsnAChR / アロステリック・リガンド / Treg / Th1 / Th2 / GTS-21 / alpha7 / DO11.10マウス / T細胞分化 / alpha7 nAChR / 抗原提示細胞 / 制御性T細胞 / エフェクターT細胞 / SLURP-1 / Th分化 / Th17 / α7 nAChR / アロステリック・リガンド / T細胞 / 分化
Outline of Final Research Achievements

We studied roles of GTS-21, an alpha7 (a7) nAChR agonist, and recombinant human type SLURP-1 (rhSLURP-1), an endogenous allosteric a7 nAChR ligand, in regulation of T cell differentiation. The differentiation was activated by culturing spleen cells from DO11.10 mice with ovalbumin (OVA) or OVA peptide (OVA-P). The effects of GTS-21 and rhSLURP-1 on T cell differentiation into regulatory T cell (Tregs) and effector T cells (Th1 and Th2) were determined by FACS or ELISA. GTS-21 inhibited the differentiation into Tregs and effector T cells under OVA activation, but facilitated the differentiation under OVA-P activation. rhSLURP-1 did not show any effect under the present experimental conditions. These results suggest that a7 nAChR activation in antigen-presenting cells prevents antigen processing leading to suppression of the differentiation while a7 nAChR activation in T cell facilitates the differentiation. No effect with rhSLURP-1 may be due to species difference.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (15 results)

All 2018 2017 2016 2015

All Journal Article (7 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 7 results,  Open Access: 4 results,  Acknowledgement Compliant: 5 results) Presentation (8 results)

  • [Journal Article] Expression and Function of the Cholinergic System in Immune Cells2017

    • Author(s)
      Fujii Takeshi、Mashimo Masato、Moriwaki Yasuhiro、Misawa Hidemi、Ono Shiro、Horiguchi Kazuhide、Kawashima Koichiro
    • Journal Title

      Frontiers in Immunology

      Volume: 8 Pages: 1085-1085

    • DOI

      10.3389/fimmu.2017.01085

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Physiological functions of the cholinergic system in immune cells2017

    • Author(s)
      Fujii Takeshi、Mashimo Masato、Moriwaki Yasuhiro、Misawa Hidemi、Ono Shiro、Horiguchi Kazuhide、Kawashima Koichiro
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 134 Issue: 1 Pages: 1-21

    • DOI

      10.1016/j.jphs.2017.05.002

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Acetylcholine released from T cells regulates intracellular Ca2+, IL-2 secretion and T cell proliferation through nicotinic acetylcholine receptor.2017

    • Author(s)
      Mashimo M, Iwasaki Y, Inoue S, Saito S, Kawashima K, Fujii T.
    • Journal Title

      Life Sci.

      Volume: 172 Pages: 13-18

    • DOI

      10.1016/j.lfs.2016.12.015

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Recent progress in revealing the biological and medical significance of the non-neuronal cholinergic system.2015

    • Author(s)
      Grando SA, Kawashima K, Kirkpatrick CJ, Kummer W, Wessler I
    • Journal Title

      Int Immunopharmacol

      Volume: 29 Pages: 1-7

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Transcriptional regulation of SLURP2, a psoriasis-associated gene, is under control of IL-22 in the skin: a special reference to the nested gene LYNX1.2015

    • Author(s)
      Moriwaki Y, Takada K, Tsuji S, Kawashima K, Misawa H
    • Journal Title

      Int immunopharmacol

      Volume: 29 Issue: 1 Pages: 71-75

    • DOI

      10.1016/j.intimp.2015.05.030

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Non-neuronal cholinergic system in regulation of immune function with a focus on 7 nAChRs.2015

    • Author(s)
      Kawashima K, Fujii T, Moriwaki Y, Misawa H, Horiguchi K
    • Journal Title

      Inter Immunopharmacol

      Volume: 印刷中 Issue: 1 Pages: 127-134

    • DOI

      10.1016/j.intimp.2015.04.015

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] IL-22/STAT3-induced increases in SLURP1 expression within psoriatic lesions exerts antimicrobial effects against Staphylococcus aureus.2015

    • Author(s)
      Moriwaki Y, Takada K, Nagasaki T, Kubo N, Ishii T, Kose K, Kageyama T, Tsuji S, Kawashima K, Misawa H
    • Journal Title

      PLoS One

      Volume: 該当なし Issue: 10 Pages: e0140750-e0140750

    • DOI

      10.1371/journal.pone.0140750

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] マウス脾臓細胞におけるT細胞の活性化がアセチルコリン受容体の発現に及ぼす影響の検討.2018

    • Author(s)
      坂口 美咲、間下 雅士、田中 菜穂子、川島 紘一郎、藤井 健志.
    • Organizer
      第138回日本薬学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Alpha7 ニコチン性アセチルコリン受容体は、抗原提示細胞の抗原提示過程を阻害しヘルパーT細胞の分化を抑制する.2018

    • Author(s)
      松井 悠理子、間下 雅士、小森 眞紗代、井上 笙子、齋藤 聖子、奥山 洋美、小野 史郎、川島 紘一郎、藤井 健志.
    • Organizer
      第138回日本薬学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Tリンパ球におけるアセチルコリンのオートクライン作用の生理的役割の解明.2017

    • Author(s)
      岩崎 有可里、間下 雅士、井上 笙子、斎藤 聖子、川島 紘一郎、藤井 健志.
    • Organizer
      第67回 日本薬学会近畿支部総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Alpha7 ニコチン性アセチルコリン受容体刺激による制御性T細胞の分化促進.2017

    • Author(s)
      祭田 絢子、間下 雅士、小森 眞紗代、松井 悠理子、小野 史郎、川島 紘一郎、奥山 洋美、森脇 康博、三澤 日出巳、藤井 健志.
    • Organizer
      第67回 日本薬学会近畿支部総
    • Related Report
      2017 Annual Research Report
  • [Presentation] Role for α7 nicotinic acetylcholine receptors in naive T cell differentiation into regulatory T cells.2016

    • Author(s)
      Kawashima K, Mashimo M, Fujii T, Moriwaki M, Misawa H, Ono S
    • Organizer
      Neuroscience 2016
    • Place of Presentation
      San Diego, CA, USA
    • Year and Date
      2016-11-11
    • Related Report
      2016 Research-status Report
  • [Presentation] 制御性 T 細胞分化におけるα 7 ニコチン性アセチルコリン受容体の役割2016

    • Author(s)
      井上笙子、斉藤聖子、間下雅士、竹島詩織、奥山洋美、小野史郎、川島紘一郎、藤井健志
    • Organizer
      第129回日本薬理学会近畿部会
    • Place of Presentation
      広島県医師会館,広島市
    • Related Report
      2016 Research-status Report
  • [Presentation] α7 ニコチン受容体シグナルは抗原提示細胞機能の抑制を介して ヘルパー T 細胞の分化誘導を阻害する2016

    • Author(s)
      井上笙子、斉藤聖子、間下雅士、竹島詩織、奥山洋美、小野史郎、川島紘一郎、藤井健志
    • Organizer
      第129回日本薬理学会近畿部会
    • Place of Presentation
      広島県医師会館,広島市
    • Related Report
      2016 Research-status Report
  • [Presentation] Tリンパ球モデル細胞MOLT3におけるアセチルコリンのオートクラインおよびパラクライン作用による細胞増殖およびIL-2の産生への影響。2015

    • Author(s)
      岩崎有可里、間下雅士、井上笙子、斎藤聖子、川島紘一郎、藤井健志
    • Organizer
      第65回日本薬学会近畿支部総会・大会
    • Place of Presentation
      大阪大谷大学,富田林市,大阪府
    • Year and Date
      2015-10-17
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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