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Molecular mechanism and regulation in patients with Sjogren's syndrome

Research Project

Project/Area Number 17K09966
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Collagenous pathology/Allergology
Research InstitutionUniversity of Tsukuba

Principal Investigator

Sumida Takayuki  筑波大学, 医学医療系, 教授 (00183054)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsシェーグレン症候群 / Th1細胞 / Treg細胞 / iPS細胞 / ムスカリン作動性アセチルコリン受容体3 / T細胞抗原受容体 / T細胞機能転換分子 / 膠原病学 / ムスカリン作働性アセチルコリン受容体3 / T細胞昨日転換分子 / ムスカリン作動性アセチルコリン受容体 / T細胞抗原病受容体
Outline of Final Research Achievements

M3R reactive Th1 cells play a crucial role in the generation of Sjogren’s syndrome(SS). In the present study, our object is to clarify the molecules which are able to change Th1 cells to Treg cells. We already generated several T-iPS cells from M3R reactive Th1 cells in patients with SS, induced DC cells from their T-iPS cells, and differentiated CD34+CD43+ progenitor stem cells form T-iPS cells in vitro. In future, we will differentiate CD34+CD43+ cells to Treg cells, and then elucidate the functional molecules which could change from Th1 cells to Treg cells. The candidate molecules should shed light on the new therapeutic approach to SS.

Academic Significance and Societal Importance of the Research Achievements

シェーグレン症候群(SS)は、ドライアイやドライマウスだけではなく全身の臓器病変を生じる自己免疫疾患である。全身の臓器病変に対する治療は、ステロイドや免疫抑制薬が主体であり、副作用として感染症、悪性腫瘍、生活習慣病、骨粗鬆症などを合併し、QOLの低下が起きてしまうことが問題となっている。本研究の意義は、SSの発症機序に基づいた治療戦略を開発するため、副作用のない疾患特異的な治療薬が創薬され患者さんのQOLの向上が期待されることである。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (25 results)

All 2020 2019 2018 2017

All Journal Article (10 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 10 results,  Open Access: 8 results) Presentation (14 results) (of which Int'l Joint Research: 5 results,  Invited: 1 results) Book (1 results)

  • [Journal Article] Allergin-1 immunoreceptor suppresses house dust mite-induced allergic airway inflammation.2020

    • Author(s)
      Miki H, Tahara-Hanaoka S, Almeida MS, Hitomi K, Shibagaki S, Kanemaru K, Lin YH, Iwata K, Miyake S, Shibayama S, Sumida T, Shibuya K, Shibuya A
    • Journal Title

      Journal of Immunology

      Volume: 204(4) Issue: 4 Pages: 753-762

    • DOI

      10.4049/jimmunol.1900180

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] RORγt antagonist improves Sj?gren's syndrome‐like sialadenitis through downregulation of CD252020

    • Author(s)
      Ono Yuko、Tsuboi Hiroto、Moriyama Masafumi、Asashima Hiromitsu、Kudo Hanae、Takahashi Hiroyuki、Honda Fumika、Abe Saori、Kondo Yuya、Takahashi Satoru、Matsumoto Isao、Nakamura Seiji、Sumida Takayuki
    • Journal Title

      Oral Diseases

      Volume: - Issue: 4 Pages: 766-777

    • DOI

      10.1111/odi.13255

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Transgenic rice seeds expressing altered peptide ligands against the M3 muscarinic acetylcholine receptor suppress experimental sialadenitis-like Sjogren’s syndrome2019

    • Author(s)
      Kudo Hanae、Tsuboi Hiroto、Asashima Hiromitsu、Takahashi Hiroyuki、Ono Yuko、Abe Saori、Honda Fumika、Kondo Yuya、Wakasa Yuhya、Takaiwa Fumio、Takano Makoto、Matsui Minoru、Matsumoto Isao、Sumida Takayuki
    • Journal Title

      Modern Rheumatology

      Volume: - Issue: 5 Pages: 1-10

    • DOI

      10.1080/14397595.2019.1664368

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Potential involvement of OX40 in the regulation of autoantibody sialylation in arthritis2019

    • Author(s)
      Izumi Kurata, Isao Matsumoto, Ayako Ohyama, Atsumu Osada, Hiroshi Ebe, Hoshimi Kawaguchi, Shunta Kaneko, Yuya Kondo, Hiroto Tsuboi, Azusa Tomioka, Hiroyuki Kaji, Takayuki Sumida
    • Journal Title

      Annals of the Rheumatic Diseases

      Volume: 78 Issue: 11 Pages: 1488-1496

    • DOI

      10.1136/annrheumdis-2019-215195

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PLD4 is a genetic determinant to systemic lupus erythematosus and involved in murine autoimmune phenotypes2019

    • Author(s)
      Akizuki S, Ishigaki K, Kochi Y, Law SM, Matsuo K, Ohmura K, Suzuki A, Nakayama M, Iizuka Y, Koseki H, Ohara O, Hirata J, Kamatani Y, Matsuda F, Sumida T, Yamamoto K, Okada Y, Mimori T, Terao C.
    • Journal Title

      Annals of the Rheumatic Diseases

      Volume: 78 Issue: 4 Pages: 509-518

    • DOI

      10.1136/annrheumdis-2018-214116

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Placenta Specific 8 Suppresses IL-18 Production through Regulation of Autophagy and Is Associated with Adult Still Disease2018

    • Author(s)
      Segawa Seiji、Kondo Yuya、Nakai Yuji、Iizuka Akira、Kaneko Shunta、Yokosawa Masahiro、Furuyama Kotona、Tsuboi Hiroto、Goto Daisuke、Matsumoto Isao、Sumida Takayuki
    • Journal Title

      The Journal of Immunology

      Volume: 201 Issue: 12 Pages: 3534-3545

    • DOI

      10.4049/jimmunol.1800667

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical practice guideline for Sj?gren’s syndrome 20172018

    • Author(s)
      Sumida Takayuki、Azuma Naoto、Moriyama Masafumi、Takahashi Hiroyuki、Asashima Hiromitsu、Honda Fumika、Abe Saori、Ono Yuko、Hirota Tomoya、Hirata Shintaro、Tanaka Yoshiya、Shimizu Toshimasa、Nakamura Hideki、Kawakami Atsushi、Sano Hajime、Ogawa Yoko、Tsubota Kazuo、Ryo Koufuchi、Saito Ichiro、Tsuboi Hiroto
    • Journal Title

      Modern Rheumatology

      Volume: 28 Issue: 3 Pages: 383-408

    • DOI

      10.1080/14397595.2018.1438093

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Splicing variant ofWDFY4augments MDA5 signalling and the risk of clinically amyopathic dermatomyositis2018

    • Author(s)
      Kochi Yuta et al.
    • Journal Title

      Annals of the Rheumatic Diseases

      Volume: 77 Issue: 4 Pages: 602-611

    • DOI

      10.1136/annrheumdis-2017-212149

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Transcriptional Regulation of CD4+ T Cell Differentiation in Experimentally Induced Arthritis and Rheumatoid Arthritis2018

    • Author(s)
      Kondo Yuya、Yokosawa Masahiro、Kaneko Shunta、Furuyama Kotona、Segawa Seiji、Tsuboi Hiroto、Matsumoto Isao、Sumida Takayuki
    • Journal Title

      Arthritis Rheumatol

      Volume: in press Issue: 5 Pages: 653-661

    • DOI

      10.1002/art.40398

    • NAID

      120007134136

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Functional Analysis of Dendritic Cells Generated from T-iPSCs from CD4+ T Cell Clones of Sj?gren's Syndrome2017

    • Author(s)
      Iizuka-Koga Mana、Asashima Hiromitsu、Ando Miki、Lai Chen-Yi、Mochizuki Shinji、Nakanishi Mahito、Nishimura Toshinobu、Tsuboi Hiroto、Hirota Tomoya、Takahashi Hiroyuki、Matsumoto Isao、Otsu Makoto、Sumida Takayuki
    • Journal Title

      Stem Cell Reports

      Volume: 8 Issue: 5 Pages: 1155-1163

    • DOI

      10.1016/j.stemcr.2017.04.010

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 高橋広行、坪井洋人、瀬川誠司、浅島弘充、安部沙織、工藤華枝、小野由湖、本田文香、近藤裕也、松本功、大津真、住田孝之2019

    • Author(s)
      シェーグレン症候群におけるM3R反応性Th1細胞由来T-iPS細胞を応用した治療戦略
    • Organizer
      第63回日本リウマチ学会総会・学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] シェーグレン症候群におけるM3R反応性Th1細胞由来T-iPS細胞を応用した治療戦略2019

    • Author(s)
      高橋広行、坪井洋人、安部沙織、小野由湖、本田文香、安藤美樹、近藤裕也、松本功、大津真、住田孝之
    • Organizer
      第28回シェーグレン症候群学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Detection of circulating M3 muscarinic acetylcholine receptor reactive Th17 cells in patients with primary Sjogren's syndrome.2019

    • Author(s)
      Abe S, Tsuboi H, Kudo H, Ono Y, Honda F, Kurata I, Yagishita M, Takahashi H, Yokosawa M, Kondo Y, Matsumoto I, Sumida T.
    • Organizer
      第63回日本リウマチ学会総会・学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] シェーグレン症候群患者末梢血中におけるM3ムスカリン作働性アセチルコリン受容体(M3R)反応性Th17細胞2019

    • Author(s)
      安部沙織、坪井洋人、本田文香、小野由湖、高橋広行、近藤裕也、松本功、住田孝之
    • Organizer
      第28回シェーグレン症候群学会学術集
    • Related Report
      2019 Annual Research Report
  • [Presentation] Detection and Clinical Significance of Circulating M3 Muscarinic Acetylcholine Receptor Reactive Th17 Cells in Patients with Primary Sjogren’s Syndrome.2019

    • Author(s)
      Abe S, Tsuboi H, Ono Y, Honda F, Kurata I, Yagishita M, Ohyama A, Takahashi H, Matsumoto A, Sumida T.
    • Organizer
      The 2019 ACR/ARHP Annual Meeting in Atlanta
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A potential role of NR4A2 overexpression in CD4+ T cells in the pathogenesis of Sjogren's Syndrome.2018

    • Author(s)
      Takahashi H, Tsuboi H, Asashima H, Hirota T, Kondo Y, Matsumoto I, Sumida T.
    • Organizer
      14th International Symposium on Sjogren's Syndrome
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] RORγt antagonis suppressed spontaneous sialadenitis in RORγt transgenic mice via inhibition of IL-17 production with increase of regulatory T cells.2018

    • Author(s)
      Ono Y, Tsuboi H, Moriyama M, Asashima H, Kudo H, Takahashi H, Kondo Y, Matsumoto I, Nakaramura S, Sumida T.
    • Organizer
      14th International Symposium on Sjogren's Syndrome
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Analysis of suppressive ability and its mechanisms of rice seeds expressing altered peptide ligands against M3 muscarinic acetylcholine receptor (M3R) induced sialadenitis.2018

    • Author(s)
      Kudo H, Tsuboi H, Asashima H, Takahashi H, Ono Y, Abe S, Kondo Y, Wakasa Y, Takaiwa F, Matsumoto I, Sumida T.
    • Organizer
      14th International Symposium on Sjogren's Syndrome
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] シェーグレン症候群患者のCD4陽性T細胞におけるNR4A2発現亢進とTh17分化2018

    • Author(s)
      高橋広行、坪井洋人、浅島弘充、近藤裕也、松本功、住田孝之
    • Organizer
      第62回日本リウマチ学会総会・学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] M3ムスカリン作働性アセチルコリン受容体(M3R) 誘導性唾液腺炎に対するaltered peptide ligand (APL)発現米の抑制効果と 作用メカニズムの解析2018

    • Author(s)
      工藤華枝、坪井洋人、浅島弘充、髙橋広行、小野由湖、安部沙織、近藤裕也、若佐雄也、高岩文雄、松本功、住田孝之
    • Organizer
      第62回日本リウマチ学会総会・学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] シェーグレン症候群 vs IgG4関連疾患:似て非なる病2018

    • Author(s)
      住田孝之
    • Organizer
      第27回シェーグレン症候群学会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] The functional analysis of dendritic cells developed from T-iPS cells-derived from a single CD4+ T cell of Sjogren’s syndrome,2017

    • Author(s)
      Asashima H, Iizuka M, Ando M, Lai C-Y, Tsuboi H, Hirota T, Takahashi H, Matsumoto I, Otsu M, Sumida T.
    • Organizer
      第61回日本リウマチ学会総会・学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] The functional analysis of dendritic cells developed from T-iPS cells-derived from a single CD4+ T cell of Sjogren’s syndrome2017

    • Author(s)
      Asashima H, Iizuka M, Ando M, Lai C-Y, Tsuboi H, Hirota T, Takahashi H, Matsumoto I, Otsu M, Sumida T
    • Organizer
      The 7th East Asian Group of Rheumatology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] シェーグレン症候群患者由来T-iPS細胞から誘導した樹状細胞の機能解析2017

    • Author(s)
      浅島弘充、飯塚麻菜、安藤美樹、頼貞儀、坪井洋人、高橋広行、松本功、大津真、住田孝之
    • Organizer
      第26回シェーグレン症候群学会学術集会
    • Related Report
      2017 Research-status Report
  • [Book] シェーグレン症候群の診断と治療マニュアル2018

    • Author(s)
      竹内勤、川上純、住田孝之
    • Total Pages
      268
    • Publisher
      診断と治療社
    • ISBN
      9784787823694
    • Related Report
      2018 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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