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Elucidation of the pathogenic mechanism of Sjogren's syndrome using a novel mouse model

Research Project

Project/Area Number 18K07075
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49030:Experimental pathology-related
Research InstitutionToho University

Principal Investigator

Tanaka Yuriko  東邦大学, 医学部, 講師 (40396685)

Co-Investigator(Kenkyū-buntansha) 小野里 磨優  東邦大学, 薬学部, 講師 (50610094)
Project Period (FY) 2018-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsシェーグレン症候群 / 自己免疫疾患モデルマウス / トリプトファン代謝 / 病原性T細胞 / インドールアミン2,3デオキシゲナーゼ
Outline of Final Research Achievements

In this study, we analyzed the pathogenesis and molecular mechanisms involved in the early phase of Sjogren's syndrome (SS) using a mouse model of the disease, which exhibits SS-like pathology from early postnatal stages. We analyzed molecular markers that fluctuate in the early phase of SS-like pathophysiology in this mouse model, and found that interferon gamma production from T cells accumulated in salivary glands of the mouse model enhanced tryptophan (Trp) metabolism and increased its metabolite, kynurenine (KYN). These findings suggest that serum KYN could be used as a marker for SS diagnosis in the early phases of the disease.

Academic Significance and Societal Importance of the Research Achievements

シェーグレン症候群 (Sjogren's syndrome : SS)は、口腔や眼の乾燥症状を主訴とする難治性の自己免疫疾患である。SS患者では、乾燥症状などの病態が進行後に受診する場合も多く、発症初期の病態を解析することは現状では不可能に近い。本研究で用いたSS疾患モデルマウスは、SSの診断に用いられる自己抗体が血清中に認められる生後8-9週齢以前の生後4週齢で、既に唾液腺、涙腺にT細胞が浸潤し、乾燥症状を呈する。したがって、本研究で得られたSS発症初期に変動する新規分子マーカーは、SS発症を早期に診断し、病気の進行を発症早期から制御する方法の開発に寄与する可能性が示唆される。

Report

(6 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
  • Research Products

    (28 results)

All 2022 2021 2020 2019 2018

All Journal Article (7 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (21 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] SATB1-dependent mitochondrial ROS production controls TCR signaling in CD4 T cells2021

    • Author(s)
      Kuwabara Taku、Ishikawa Fumio、Ikeda Masataka、Ide Tomomi、Kohwi-Shigematsu Terumi、Tanaka Yuriko、Kondo Motonari
    • Journal Title

      Life Science Alliance

      Volume: 4 Issue: 11 Pages: e202101093-e202101093

    • DOI

      10.26508/lsa.202101093

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Increased Indoleamine 2,3-Dioxygenase Levels at the Onset of Sjogren’s Syndrome in SATB1-Conditional Knockout Mice2021

    • Author(s)
      Tanaka Yuriko、Onozato Mayu、Mikami Tetuo、Kohwi-Shigematsu Terumi、Fukushima Takeshi、Kondo Motonari
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 18 Pages: 10125-10125

    • DOI

      10.3390/ijms221810125

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] High CD4+ T-Cell/B-Cell Ratio in the Paranasal Sinus Mucosa of Patients with Eosinophilic Chronic Rhinosinusitis2020

    • Author(s)
      Akiko Inoue, Yuriko Tanaka, Shinya Ohira, Kentaro Matsuura, Motonari Kondo, Kota Wada
    • Journal Title

      International Archives of Otorhinolaryngology

      Volume: 10 Issue: 03 Pages: 1-1

    • DOI

      10.1055/s-0040-1715587

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tissue Damage Caused by Impaired Phagocytosis of Dead Cells: A Previously Unrecognized Adverse Effect Contributing to the Pathogenesis of γδ T Cells in Legionella Pneumonia2020

    • Author(s)
      Chiaki Kajiwara, Soichiro Kimura, Yuriko Tanaka, Yoshikiyo Akasaka, Yoshikazu Ishii, and Kazuhiro Tateda
    • Journal Title

      Immunohorizons

      Volume: 14 Pages: 402-414

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] SATB1によるT細胞分化と免疫寛容の制御2019

    • Author(s)
      田中ゆり子, 近藤元就
    • Journal Title

      週間医学のあゆみ

      Volume: 268 Pages: 1064-1068

    • Related Report
      2018 Research-status Report
  • [Journal Article] SATB1欠損により発症する自己免疫疾患2018

    • Author(s)
      田中ゆり子, 近藤元就
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 3 Pages: 307-312

    • NAID

      40021674581

    • Related Report
      2018 Research-status Report
  • [Journal Article] Amino acid analyses of the exosome-eluted fractions from human serum by HPLC with fluorescence detection.2018

    • Author(s)
      Onozato M, Tanaka Y, Arita M, Sakamoto T, Ichiba H, Sadamoto K, Kondo M, Fukushima T
    • Journal Title

      Practical Laboratory Medicine

      Volume: 12 Pages: e00099-e00099

    • DOI

      10.1016/j.plabm.2018.e00099

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] シェーグレン症候群疾患モデルマウスにおけるB細胞 活性化機構の解析2022

    • Author(s)
      田中ゆり子, 井上彰子, 近藤元就
    • Organizer
      第30回 日本シェーグレン症候群学会学 術集会(石川県 金沢市)
    • Related Report
      2022 Annual Research Report
  • [Presentation] Functional analyses of pathogenic T cells in autoimmune prone mice2022

    • Author(s)
      Tanaka Y, Inoue A, Naito T , Kuwabara T, Ise M , Kohwi-Shigematsu T, Kondo M
    • Organizer
      The 51st Annual Meeting of The Japanese Society for Immunology(熊本市)
    • Related Report
      2022 Annual Research Report
  • [Presentation] IL-7 regulates the expression of CD69 and CD103 on TRM cells in skin.2022

    • Author(s)
      Ise M, Kuwabara T, Tanaka Y, Naito T, Kondo M
    • Organizer
      The 51st Annual Meeting of The Japanese Society for Immunology(熊本市)
    • Related Report
      2022 Annual Research Report
  • [Presentation] SATB1-dependent mitochondrial ROS production controls TCR signaling in CD4 T cells2022

    • Author(s)
      Taku Kuwabara, Marii Ise, Taku Naito, Yuriko Tanaka, Motonari Kondo
    • Organizer
      The 51st Annual Meeting of The Japanese Society for Immunology(熊本市)
    • Related Report
      2022 Annual Research Report
  • [Presentation] SATB1遺伝子欠損マウスに生じる自己免疫性唾液腺障害の病態解析2022

    • Author(s)
      近藤 元就, 小野里 磨優, 桑原 卓, 福島 健, 田中 ゆり子
    • Organizer
      第18回 東邦大学5学部合同学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] 自己免疫疾患モデルマウス病原性T細胞による組織障害メカニズムの解析2021

    • Author(s)
      田中ゆり子, 井上彰子, 近藤元就
    • Organizer
      Kyoto T cell conference 第30回学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] シェーグレン症候群疾患モデルマウス病原性T細胞による唾液腺組織障害機構の解析2021

    • Author(s)
      田中ゆり子、井上彰子、近藤元就
    • Organizer
      第29回 日本シェーグレン症候群学会学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] Satb1 regulates thymocyte trafficking after positive selection.2021

    • Author(s)
      Taku Naito, Yuriko Tanaka, Taku Kuwabara, Marii Ise, Motonari Kondo
    • Organizer
      The 50th Annual Meeting of The Japanese Society for Immunology
    • Related Report
      2021 Research-status Report
  • [Presentation] An early serum marker for Sjogren’s syndrome in SATB1 deficient mice2021

    • Author(s)
      Yuriko Tanaka, Akiko Inoue, Taku Kuwabara, Taku Naito, Marii Ise, Motonari Kondo
    • Organizer
      The 50th Annual Meeting of The Japanese Society for Immunology
    • Related Report
      2021 Research-status Report
  • [Presentation] More severe ECRS patients produce more TSLP in the paranasal sinus mucosa2020

    • Author(s)
      Akiko Inoue, Yuriko Tanaka, Motonari Kondo, Hidehito Matsui, Takara Nakazawa, Shinya Ohira, Hiroshi Osafune, Kota Wada
    • Organizer
      JSA/WAO Joint Congress 2020
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Sjogren's syndrome疾患モデルマウスの病態解析 -発症初期新規分子マーカーの探索-2019

    • Author(s)
      田中 ゆり子、小野里 磨優、井上 彰子、福島 健、近藤 元就
    • Organizer
      東邦大学5学部合同学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Sjogren’s syndrome 疾患モデルマウス血清中代謝産物の解析. 日本トリプトファン研究会2019

    • Author(s)
      田中 ゆり子,小野里 磨優,近藤 元就,福島 健
    • Organizer
      日本トリプトファン研究会
    • Related Report
      2019 Research-status Report
  • [Presentation] シェーグレン症候群疾患モデルマウスの病態解析と発症初期新規分子マーカーの探索2019

    • Author(s)
      田中ゆり子, 井上彰子, 小野里磨優, 福島健, 近藤元就
    • Organizer
      第28回 日本シェーグレン症候群学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] LC-MS/MS によるシェーグレン症候群疾患モデルマウス血清中 L-トリプトファン及び L-キヌレニンの定量2019

    • Author(s)
      小野里 磨優, 田中 ゆり子, 井上 彰子, 近藤 元就, 福島 健
    • Organizer
      第32回 バイオメディカル分析科学シンポジウム(BMAS2019)
    • Related Report
      2019 Research-status Report
  • [Presentation] Lack of SATB1 leads to Sjogren's syndrome like autoimmune manifestations in mice.2019

    • Author(s)
      Yuriko Tanaka, Akiko Inoue, Taku Kuwabara, Taku Naito, Motonari Kondo
    • Organizer
      The 48th Annual Meeting of The Japanese Society for Immunology
    • Related Report
      2019 Research-status Report
  • [Presentation] Mitochondrial respiration is critical for TCR signaling via an oxidative inactivation of phosphatase.2019

    • Author(s)
      Taku Kuwabara, Marii Ise, Taku Naito, Yuriko Tanaka, Motonari Kondo
    • Organizer
      The 42nd annual meeting of the molecular biology society of Japan
    • Related Report
      2019 Research-status Report
  • [Presentation] Lack of SATB1 leads to Sjogren's syndrome like autoimmune manifestations in mice.2019

    • Author(s)
      Yuriko Tanaka, Akiko Inoue, Taku Naito, Taku Kuwabara, Motonari Kondo
    • Organizer
      52nd Annual Meeting Of The Society For Leukocyte Biology
    • Related Report
      2019 Research-status Report
  • [Presentation] SATB1遺伝子欠損マウスにおけるシェーグレン症候群発症機構の解析2018

    • Author(s)
      田中ゆり子, Ujjal Bhawal, Fengzhu Zhang, 近藤元就
    • Organizer
      The 60th Annual meeting of Japanese Association for Oral Biology
    • Related Report
      2018 Research-status Report
  • [Presentation] シェーグレン症候群の新しい動物モデル2018

    • Author(s)
      田中ゆり子, 井上彰子, 近藤元就
    • Organizer
      第27回 シェーグレン症候群学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] An analysis of pathophysiology of Sjogren's syndrome in SATB1 deficient mice2018

    • Author(s)
      Yuriko Tanaka, Akiko Inoue, Taku Kuwabara, Taku Naito, Motonari Kondo
    • Organizer
      The 47th Annual Meeting of The Japanese Society for Immunology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Mitochondrial transcription factor A rescues defect in T cell receptor responsiveness in SATB1 deficient mice.2018

    • Author(s)
      Taku Kuwabara, Fumio Ishikawa, Yuriko Tanaka, Taku Naito, Motonari Kondo
    • Organizer
      The 47th Annual meeting of the Japanese society for Immunology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2024-01-30  

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