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Analysis of CD8+CD26-positive/negative T cell subsets for the development of an innovative therapy and elucidating the pathophysiology of refractory autoimmune diseases

Research Project

Project/Area Number 26860760
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Collagenous pathology/Allergology
Research InstitutionJuntendo University

Principal Investigator

Hatano Ryo  順天堂大学, 医学(系)研究科(研究院), 特任研究員 (30638789)

Research Collaborator ISHII Tomonori  
SEKIGAWA Iwao  
Project Period (FY) 2014-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsCD26/DPPIV / T細胞 / SLE / 自己免疫疾患 / 細胞傷害性T細胞 / 共刺激分子 / ヒト免疫 / 共刺激 / 細胞傷害活性 / IL-10 / CD26
Outline of Final Research Achievements

CD26 is a T cell costimulatory molecule, and CD26+ T cells have been suggested to be involved in the pathophysiology of diverse autoimmune diseases. Since the role of CD26 in the pathophysiology of SLE still remains to be elucidated, our objective is to characterize the CD26-positive or negative T cell subsets in SLE patients. Human CD4+ or CD8+ T cells were purified from PBMCs of SLE patients or healthy adult volunteers, and we examined the phenotypes of CD26-positive or negative subsets. In addition to CD8+CD26nega T cells, CD4+CD26nega T cells were also markedly increased in SLE patients, and these cells exhibited CD28negaCD57+PerforinhiGranzyme Bhi cytotoxic potential. It takes more than 24 months for the patients with a large number of these subsets to reduce the daily dose of prednisolone to less than 10 mg after the initial treatment, strongly suggesting that CD26nega cytotoxic T cells are involved in the pathophysiology of steroid-resistant SLE.

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (33 results)

All 2018 2017 2016 2015 2014

All Journal Article (15 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 15 results,  Open Access: 11 results,  Acknowledgement Compliant: 5 results) Presentation (12 results) (of which Int'l Joint Research: 1 results) Book (2 results) Patent(Industrial Property Rights) (4 results)

  • [Journal Article] Establishment of intestinal epithelial cell line derived from fetal mouse colon and its immune-related characteristics - Comparison with mouse small intestinal epithelial cell line -.2018

    • Author(s)
      Iwamoto T, Totsuka M, Yamada K, Emoto T, Hatano R, Shimizu M.
    • Journal Title

      Cytotechnology

      Volume: in press

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A novel role for CD26/dipeptidyl peptidase IV as a therapeutic target in selected immune disorders and cancers.2018

    • Author(s)
      Ohnuma K, Hatano R, Komiya E, Otsuka H, Itoh T, Iwao N, Kaneko Y, Yamada T, Dang NH, Morimoto C.
    • Journal Title

      Front Biosci

      Volume: in press

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A possible role for CD26/DPPIV enzyme activity in the regulation of psoriatic pruritus2017

    • Author(s)
      Komiya, E. Hatano, R. Otsuka, H. Itoh, T. Yamazaki, H. Yamada, T. Dang, N. H. Tominaga, M. Suga, Y. Kimura, U. Takamori, K. Morimoto, C. Ohnuma, K.
    • Journal Title

      J Dermatol Sci

      Volume: 印刷中 Issue: 3 Pages: 212-221

    • DOI

      10.1016/j.jdermsci.2017.03.005

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Role of IL-26+CD26+CD4 T Cells in Pulmonary Chronic Graft-Versus-Host Disease and Treatment with Caveolin-1-Ig Fc Conjugate2016

    • Author(s)
      Ohnuma, K. Hatano, R. Itoh, T. Iwao, N. Dang, N. H. Morimoto, C.
    • Journal Title

      Crit Rev Immunol

      Volume: 36 Issue: 3 Pages: 239-267

    • DOI

      10.1615/critrevimmunol.2016018772

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Establishment of anti-mesothelioma monoclonal antibodies2016

    • Author(s)
      Mizutani N, Abe M, Matsuoka S, Kajino K, Wakiya M, Ohtsuji N, Hatano R, Morimoto C, Hino O
    • Journal Title

      BMC Res Notes

      Volume: 9 Issue: 1 Pages: 324-324

    • DOI

      10.1186/s13104-016-2128-x

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibition of VEGF-dependent angiogenesis by the anti-CD82 monoclonal antibody 4F9 through regulation of lipid raft microdomains2016

    • Author(s)
      Nomura, S. Iwata, S. Hatano, R. Komiya, E. Dang, N. H. Iwao, N. Ohnuma, K. Morimoto, C.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 474 Issue: 1 Pages: 111-7

    • DOI

      10.1016/j.bbrc.2016.04.081

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] DPP4 in anti-tumor immunity: going beyond the enzyme.2015

    • Author(s)
      Ohnuma K, Hatano R, Morimoto C.
    • Journal Title

      Nat Immunol.

      Volume: 16 Issue: 8 Pages: 791-2

    • DOI

      10.1038/ni.3210

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Role of Cas-L/NEDD9 as a Regulator of Collagen-induced Arthritis in a Murine Model2015

    • Author(s)
      Tomoki Katayose, Satoshi Iwata, Naoki Oyaizu, Osamu Hosono, Taketo Yamada, Nam H Dang, Ryo Hatano, Hirotoshi Tanaka, Kei Ohnuma, Chikao Morimoto
    • Journal Title

      Biochem Bilphys Res Commun

      Volume: 印刷中 Issue: 4 Pages: 1069-75

    • DOI

      10.1016/j.bbrc.2015.03.156

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Modulation of immunological responses and amelioration of collagen-induced arthritis by the novel roxithromycin derivative 5-I.2015

    • Author(s)
      Otsuki N, Iwata S, Yamada T, Hosono O, Dang NH, Hatano R, Ohnuma K, Morimoto C.
    • Journal Title

      Mod Rheumatol.

      Volume: 25 Issue: 4 Pages: 562-70

    • DOI

      10.3109/14397595.2014.983262

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Regulation of Pulmonary Graft-versus-Host Disease by IL-26+CD26+CD4 T Lymphocytes.2015

    • Author(s)
      Ohnuma K, Hatano R, Aune TM, Otsuka H, Iwata S, Dang NH, Yamada T, Morimoto C.
    • Journal Title

      J Immunol

      Volume: 194(8) Issue: 8 Pages: 3697-712

    • DOI

      10.4049/jimmunol.1402785

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] CD26-mediated induction of EGR2 and IL-10 as potential regulatory mechanism for CD26 costimulatory pathway.2015

    • Author(s)
      Hatano R, Ohnuma K, Otsuka H, Komiya E, Taki I, Iwata S, Dang NH, Okumura K, Morimoto C.
    • Journal Title

      J Immunol.

      Volume: Vol 194 Issue: 3 Pages: 960-72

    • DOI

      10.4049/jimmunol.1402143

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparison of Two Commercial ELISAs against an In-House ELISA for Measuring Soluble CD26 in Human Serum.2015

    • Author(s)
      Ohnuma K, Saito T, Hatano R, Hosono O, Iwata S, Dang NH, Ninomiya H, Morimoto C.
    • Journal Title

      J Clin Lab Anal.

      Volume: Vol 29 Issue: 2 Pages: 106-11

    • DOI

      10.1002/jcla.21736

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] CD26-mediated regulation of periostin expression contributes to migration and invasion of malignant pleural mesothelioma cells.2014

    • Author(s)
      Komiya E, Ohnuma K, Yamazaki H, Hatano R, Iwata S, Okamoto T, Dang NH, Yamada T, Morimoto C.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: Vol 447 Issue: 4 Pages: 609-15

    • DOI

      10.1016/j.bbrc.2014.04.037

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Regulation of somatostatin receptor 4-mediated cytostatic effects by CD26 in malignant pleural mesothelioma.2014

    • Author(s)
      Yamamoto J, Ohnuma K, Hatano R, Okamoto T, Komiya E, Yamazaki H, Iwata S, Dang NH, Aoe K, Kishimoto T, Yamada T, Morimoto C.
    • Journal Title

      Br J Cancer.

      Volume: Vol 110 Issue: 9 Pages: 2232-45

    • DOI

      10.1038/bjc.2014.151

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Grassypeptolides as natural inhibitors of dipeptidyl peptidase 8 and T-cell activation.2014

    • Author(s)
      Kwan JC, Liu Y, Ratnayake R, Hatano R, Kuribara A, Morimoto C, Ohnuma K, Paul VJ, Ye T, Luesch H.
    • Journal Title

      Chembiochem.

      Volume: Vol 15 Issue: 6 Pages: 799-804

    • DOI

      10.1002/cbic.201300762

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 急性GVHDマウスモデルにおけるHMGB1の動態に関する検討.2018

    • Author(s)
      岩尾憲明、大沼圭、大塚春奈、波多野良、古宮栄利子、伊藤匠、森本幾夫.
    • Organizer
      第40回日本造血細胞移植学会、札幌市教育文化会館(北海道札幌市)
    • Related Report
      2017 Annual Research Report
  • [Presentation] CD26/DPPIV regulates mechanical itch in a mechanistically distinct manner from chemical itch.2017

    • Author(s)
      Eriko Komiya, Ryo Hatano, Haruna Otsuka, Takumi Itoh, Hiroto Yamazaki, Mitsutoshi Tominaga, Kenji Takamori, Kei Ohnuma, Chikao Morimoto.
    • Organizer
      第42回日本研究皮膚科学会、高知市文化プラザかるぽーと(高知県高知市)
    • Related Report
      2017 Annual Research Report
  • [Presentation] IL-26 facilitates angiogenesis and skin inflammation via inducing FGF2 production in a murine model of imiquimod-induced psoriasis.2017

    • Author(s)
      Takumi Itoh, Ryo Hatano, Haruna Otsuka, Noriaki Iwao, Satoshi Iwata, Taketo Yamada, Chikao Morimoto.
    • Organizer
      第46回日本免疫学会、仙台国際センター(宮城県仙台市)
    • Related Report
      2017 Annual Research Report
  • [Presentation] The regulation of pruritus in psoriasis and atopic dermatitis -a possible role for CD26/DPPIV.2017

    • Author(s)
      Eriko Komiya, Ryo Hatano, Haruna Otsuka, Takumi Itoh, Hiroto Yamazaki, Taketo Yamada, Yasushi Suga, Utako Kimura, Mitsutoshi Tominaga, Kenji Takamori, Kei Ohnuma, Chikao Morimoto.
    • Organizer
      9th World Congress on Itch, Novotel Centrum, Wroclaw, Poland
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 全身性エリテマトーデスのステロイド治療抵抗性とCD26陰性T細胞サブセットとの関係性について.2017

    • Author(s)
      波多野良、大沼圭、石井智徳、岩田哲史、奥村康、関川巖、森本幾夫.
    • Organizer
      第61回日本リウマチ学会、福岡国際会議場(福岡県福岡市)
    • Related Report
      2017 Annual Research Report
  • [Presentation] CD26/DPPIV-mediated regulation of pruritus in psoriasis.2016

    • Author(s)
      Eriko Komiya, Ryo Hatano, Haruna Otsuka, Takumi Itoh, Taketo Yamada, Mitsutoshi Tominag, Kenji Takamori, Kei Ohnuma, Chikao Morimoto.
    • Organizer
      第41回研究皮膚科学会
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2016-11-09
    • Related Report
      2016 Research-status Report
  • [Presentation] 乾癬においてCD26/DPPIVはsubstance Pの切断を促進してかゆみを調節する.2016

    • Author(s)
      古宮栄利子, 波多野良, 大塚春奈, 伊藤匠, 山田健人, 冨永光俊, 高森建二, 大沼圭, 森本幾夫.
    • Organizer
      第31回日本乾癬学会
    • Place of Presentation
      ホテル東日本宇都宮(栃木県宇都宮市)
    • Year and Date
      2016-09-02
    • Related Report
      2016 Research-status Report
  • [Presentation] CD26陽性T細胞サブセットに基づく全身性エリテマトーデスの病態解析.2016

    • Author(s)
      波多野良, 大沼圭, 石井智徳, 岩田哲史, 奥村康, 関川巖, 森本幾夫.
    • Organizer
      第60回日本リウマチ学会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-04-21
    • Related Report
      2016 Research-status Report
  • [Presentation] Anti-interleukin-26 therapy for lung fibrosis of GVHD.2015

    • Author(s)
      Ryo Hatano, Taketo Yamada, Haruna Otsuka, Eriko Komiya, Noriaki Iwao, Ko Okumura, Chikao Morimoto, Kei Ohnuma.
    • Organizer
      第77回日本血液学会.
    • Place of Presentation
      ホテル日航金沢(石川県金沢市)
    • Year and Date
      2015-10-16
    • Related Report
      2015 Research-status Report
  • [Presentation] T細胞共刺激分子CD26に基づく全身性エリテマトーデスの病態および疾患活動性の新規バイオマーカーの探索.2015

    • Author(s)
      波多野良, 大沼圭, 岩田哲史, 石井智徳, 関川巖, 森本幾夫.
    • Organizer
      第59回日本リウマチ学会.
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-04-23
    • Related Report
      2015 Research-status Report
  • [Presentation] IL-10産生誘導によるCD26共刺激経路のnegative feedback機構の解析.2014

    • Author(s)
      波多野良, 大沼圭, 岩田哲史, 石井智徳, 関川巖, 森本幾夫.
    • Organizer
      第58回日本リウマチ学会.
    • Place of Presentation
      グランドプリンスホテル新高輪 (東京都港区)
    • Year and Date
      2014-04-24 – 2014-04-26
    • Related Report
      2014 Research-status Report
  • [Presentation] DPP4阻害薬の服用によって誘発される多関節症とそのバイオマーカー.2014

    • Author(s)
      大沼圭, 斎藤辰彦, 波多野良, 岩田哲史, 鈴木博史, 森本幾夫.
    • Organizer
      第58回日本リウマチ学会.
    • Place of Presentation
      グランドプリンスホテル新高輪 (東京都港区)
    • Year and Date
      2014-04-24 – 2014-04-26
    • Related Report
      2014 Research-status Report
  • [Book] Advances in Medicine and Biology2018

    • Author(s)
      Hatano R, Ohnuma K, Yamada T, Okamoto T, Komiya E, Otsuka H, Itoh T, Yamazaki H, Iwao N, Kaneko Y, Dang NH, Morimoto C.
    • Total Pages
      44
    • Publisher
      Nova Science Publishers, Inc., Hauppauge, NY
    • Related Report
      2017 Annual Research Report
  • [Book] Horizons in Cancer Research.2017

    • Author(s)
      Ohnuma K, Hatano R, Yamazaki H, Kaneko Y, Dang NH, Morimoto C.
    • Total Pages
      34
    • Publisher
      Nova Science Publishers, Inc.
    • Related Report
      2016 Research-status Report
  • [Patent(Industrial Property Rights)] 抗ヒトCD26モノクローナル抗体.2018

    • Inventor(s)
      森本幾夫、波多野良、山田健人、大沼圭.
    • Industrial Property Rights Holder
      学校法人順天堂、学校法人埼玉医科大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-049308
    • Filing Date
      2018
    • Related Report
      2017 Annual Research Report
  • [Patent(Industrial Property Rights)] 抗ヒトIL-26抗体.2017

    • Inventor(s)
      森本幾夫、波多野良、大沼圭、伊藤匠.
    • Industrial Property Rights Holder
      学校法人順天堂
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2017-231439
    • Filing Date
      2017
    • Related Report
      2017 Annual Research Report
  • [Patent(Industrial Property Rights)] 抗CD10抗体.2017

    • Inventor(s)
      水谷奈津子、阿部雅明、松岡周二、樋野興夫、大辻奈穂美、波多野良.
    • Industrial Property Rights Holder
      学校法人順天堂、日本抗体医薬株式会社
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017
    • Related Report
      2017 Annual Research Report
  • [Patent(Industrial Property Rights)] 免疫抑制剤.2014

    • Inventor(s)
      森本幾夫, 大沼圭, 波多野良.
    • Industrial Property Rights Holder
      順天堂大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2014-199260
    • Filing Date
      2014-09-29
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2019-03-29  

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