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Investigation of the pathogenic mechanism of Sjogren's syndrome based on intracellular metabolism and establishment of novel therapeutic strategies

Research Project

Project/Area Number 17K19759
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Oral Science and related fields
Research InstitutionNihon University (2020-2022)
The University of Tokushima (2017-2019)

Principal Investigator

YAMAMOTO Akiko  日本大学, 歯学部, 助教 (70452646)

Project Period (FY) 2017-06-30 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2017: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Keywords自己免疫疾患 / シェーグレン症候群 / T細胞 / CD4陽性T細胞 / 代謝 / 細胞内代謝
Outline of Final Research Achievements

In Sjogren's syndrome, there is a marked lymphocytic infiltrate around the lacrimal and salivary glands. Most of these lymphocytes are activated autoreactive T cells, and the exocrine function of the lacrimal and salivary glands is damaged by these activated autoreactive T cells. However, the mechanism regulating the activation of autoreactive T cells is still unknown.
Therefore, we performed a quantitative proteomic analysis of T cells isolated from lymphoid organs of both Sjogren's syndrome model mice and normal mice, and selected a molecule suggested to be associated with the pathogenesis of Sjogren's syndrome and generated a gene knockout mouse for this molecule.

Academic Significance and Societal Importance of the Research Achievements

本法におけるシェーグレン症候群の患者総数は約10万人と推定されている。これまで種々の研究が行われてきたにもかかわらず、治療法は乾燥症状に対する対症療法のみで根本的治療法はまだ開発されていない。本研究では、涙腺および唾液腺を傷害する主な免疫細胞であるT細胞を対象とした定量的プロテオミクス解析を実施し、病態の増悪と相関する発現変動を示す分子を同定した。当該分子がシェーグレン症候群の有効な治療標的分子となり得る可能性は高く、臨床的波及効果は高いと考えられる。

Report

(7 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (25 results)

All 2023 2022 2021 2019 2018 2017 Other

All Journal Article (11 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 11 results,  Open Access: 9 results,  Acknowledgement Compliant: 1 results) Presentation (12 results) Remarks (2 results)

  • [Journal Article] Regulatory mechanisms of mitochondrial calcium uptake by the calcium uniporter complex2023

    • Author(s)
      Akiko Yamada, Akira Watanabe, Takenori Yamamoto
    • Journal Title

      Biophysics and Physicobiology

      Volume: 20 Issue: 1 Pages: n/a

    • DOI

      10.2142/biophysico.bppb-v20.0004

    • ISSN
      2189-4779
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Quantitative analysis of mitochondrial calcium uniporter (MCU) and essential MCU regulator (EMRE) in mitochondria from mouse tissues and HeLa cells2022

    • Author(s)
      Akira Watanabe, Kousuke Maeda, Atsushi Nara, Mei Hashida, Mizune Ozono, Ayaka Nakao, Akiko Yamada, Yasuo Shinohara and Takenori Yamamoto
    • Journal Title

      FEBS Open Bio

      Volume: 12 Issue: 4 Pages: 811-826

    • DOI

      10.1002/2211-5463.13371

    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The molecular mechanisms of mitochondrial calcium ion channel, calcium uniporter2021

    • Author(s)
      Takenori Yamamoto, Akiko (Yamada) Yamamoto, Yasuo Shinohara, Akira Watanabe
    • Journal Title

      Seibutsubutsuri

      Volume: in press

    • NAID

      130008045192

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Achaete-Scute Homologue 2-Regulated Follicular Helper T Cells Promote Autoimmunity in a Murine Model for Sjogren Syndrome.2019

    • Author(s)
      Otsuka K, Yamada A, Saito M, Ushio A, Sato M, Kisoda S, Shao W, Tsunematsu T, Kudo Y, Arakaki R, Ishimaru N.
    • Journal Title

      Am J Pathol.

      Volume: 189(12) Issue: 12 Pages: 2414-2427

    • DOI

      10.1016/j.ajpath.2019.08.008

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Long-term polarization of alveolar macrophages to a profibrotic phenotype after inhalation exposure to multi-wall carbon nanotubes.2018

    • Author(s)
      Otsuka K, Yamada K, Taquahashi Y, Arakaki R, Ushio A, Saito M, Yamada A, Tsunematsu T, Kudo Y, Kanno J, Ishimaru N.
    • Journal Title

      PLoS One.

      Volume: 13(10) Issue: 10 Pages: 1-18

    • DOI

      10.1371/journal.pone.0205702

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] CCL22-Producing Resident Macrophages Enhance T Cell Response in Sjogren's Syndrome.2018

    • Author(s)
      Ushio A, Arakaki R, Otsuka K, Yamada A, Tsunematsu T, Kudo Y, Aota K, Azuma M, Ishimaru N.
    • Journal Title

      Front Immunol.

      Volume: 9 Pages: 2594-2594

    • DOI

      10.3389/fimmu.2018.02594

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] NF-κB2 Controls the Migratory Activity of Memory T Cells by Regulating Expression of CXCR4 in a Mouse Model of Sjogren's Syndrome.2017

    • Author(s)
      Kurosawa M, Arakaki R, Yamada A, Tsunematsu T, Kudo Y, Sprent J, Ishimaru N.
    • Journal Title

      Arthritis Rheumatol.

      Volume: 69 Issue: 11 Pages: 2193-2202

    • DOI

      10.1002/art.40230

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Pathological Analysis of Ocular Lesions in a Murine Model of Sjogren's Syndrome.2017

    • Author(s)
      Ushio A, Arakaki R, Eguchi H, Hotta F, Yamada A, Kudo Y, Ishimaru N
    • Journal Title

      Int J Mol Sci.

      Volume: 18 Issue: 6 Pages: 1209-1209

    • DOI

      10.3390/ijms18061209

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Establishment and characterization of a clear cell odontogenic carcinoma cell line with EWSR1-ATF1 fusion gene.2017

    • Author(s)
      Kujiraoka S, Tsunematsu T, Sato Y, Yoshida M, Tohyama R, Tanaka M, Kobayashi Y, Kondo T, Ushio A, Otsuka K, Kurosawa M, Saito M. Yamada A, Arakaki R, Nagai H, Nikai H, Takeuchi K, Nagao T, Miyamoto Y, Ishimaru N, Kudo Y.
    • Journal Title

      Oral Oncol.

      Volume: 69 Pages: 46-55

    • DOI

      10.1016/j.oraloncology.2017.04.003

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dual role of Fas/FasL-mediated signal in peripheral immune tolerance.2017

    • Author(s)
      Yamada A, Arakaki R, Saito M, Kudo Y, Ishimaru N.
    • Journal Title

      Front in Immunol.

      Volume: 8 Pages: 403-403

    • DOI

      10.3389/fimmu.2017.00403

    • NAID

      120006374401

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Unique Phenotypes and Functions of Follicular Helper T Cell and Regulatory T Cell in Sjogren's Syndrome.2017

    • Author(s)
      Saito M, Otsuka K, Ushio A, Yamada A, Arakaki R, Kudo Y, Ishimaru N
    • Journal Title

      Curr Rheumatol Rev.

      Volume: 印刷中

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] カリオフェリンを介した IL-1a の核移行メカニズムの解明2022

    • Author(s)
      山本安希子,和氣清尊,角田麻里子,福井 怜,浅野正岳
    • Organizer
      第64回歯科基礎医学会学術大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] IL-1aの核内輸送における分子制御機構の解明2022

    • Author(s)
      和氣清尊,山本安希子,今岡紗耶,角田麻里子,浅野正岳
    • Organizer
      第111回日本病理学会総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 非アルコール性脂肪肝炎モデルマウスにおけるミトコンドリアの機能解析2021

    • Author(s)
      山本安希子、奈良篤、石丸直澄、山本武範、浅野正岳
    • Organizer
      第110回日本病理学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] シェーグレン症候群モデルマウスの唾液腺マクロファージと病態への関与2017

    • Author(s)
      牛尾 綾, 新垣 理恵子, 山田 安希子, 大塚 邦紘, 黒澤 実愛, 工藤 保誠, 石丸 直澄
    • Organizer
      第16回四国免疫フォーラム
    • Related Report
      2017 Research-status Report
  • [Presentation] ミトコンドリアカルシウムユニポーター(MCU)の構造と機能の相関解析2017

    • Author(s)
      大園 瑞音, 山本 武範, 渡辺 朗, 山田 安希子, 廣島 佑香, 寺田 弘, 篠原 康雄
    • Organizer
      第9回日本生物物理学会中国四国支部大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Chronic influence of Multi-walled carbon nanotubes (MWCNT) on immune system2017

    • Author(s)
      新垣 理恵子, 山田 耕一, 齋藤 雅子, 大塚 邦紘, 山田 安希子, 常松 貴明, 工藤 保誠, 菅野 純, 石丸 直澄
    • Organizer
      第106回日本病理学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 胎児性癌細胞におけるユビキチンプロテアソーム経路による未分化性維持機構,2017

    • Author(s)
      常松 貴明, 工藤 保誠, 山田 安希子, 新垣 理恵子, 小川 博久, 常山 幸一, 石丸 直澄
    • Organizer
      第106回日本病理学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] シェーグレン症候群の唾液腺におけるマクロファージサブセットと病態への関与2017

    • Author(s)
      牛尾 綾, 新垣 理恵子, 山田 安希子, 大塚 邦紘, 鯨岡 聡子, 常松 貴明, 工藤 保誠, 石丸 直澄
    • Organizer
      第106回日本病理学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 歯原性明細胞癌細胞株の樹立とその性状解析2017

    • Author(s)
      鯨岡 聡子, 工藤 保誠, 常松 貴明, 牛尾 綾, 大塚 邦紘, 山田 安希子, 新垣 理恵子, 石丸 直澄
    • Organizer
      第106回日本病理学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 口腔癌におけるPeriostinスプライシングバリアントの新たな役割2017

    • Author(s)
      梅田 将旭, 常松 貴明, 齋藤 雅子, 山田 安希子, 新垣 理恵子, 工藤 保誠, 石丸 直澄
    • Organizer
      第106回日本病理学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] シェーグレン症候群モデルマウスにおける濾胞ヘルパーT細胞の解析2017

    • Author(s)
      大塚 邦紘, 山田 安希子, 齋藤 雅子, 牛尾 綾, 黒澤 実愛, 鯨岡 聡子, 常松 貴明, 工藤 保誠, 新垣 理恵子, 石丸 直澄
    • Organizer
      第106回日本病理学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] シェーグレン症候群における制御性T細胞の分化誘導メカニズムの解明2017

    • Author(s)
      山田 安希子、新垣 理恵子、牛尾 綾、大塚 邦紘、黒澤 美愛、工藤 保誠、石丸 直澄
    • Organizer
      第106回日本病理学会総会
    • Related Report
      2017 Research-status Report
  • [Remarks] 徳島大学口腔分子病態学分野

    • URL

      https://www.tokushima-u.ac.jp/dent/research/sousei_kagaku/oral_medicine/illness_state/

    • Related Report
      2018 Research-status Report
  • [Remarks] 徳島大学口腔分子病態学 研究室紹介

    • URL

      http://www.tokushima-u.ac.jp/dent/research/sousei_kagaku/oral_medicine/illness_state/research_introduce/

    • Related Report
      2017 Research-status Report

URL: 

Published: 2017-07-21   Modified: 2024-01-30  

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