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Identification of T cell pathway causing the acquired aplastic anemia

Research Project

Project/Area Number 17K16184
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Hematology
Research InstitutionKanazawa University

Principal Investigator

Hosokawa Kohei  金沢大学, 附属病院, 助教 (10786239)

Research Collaborator Hosomichi Kazuyoshi  
Young Neal. S.  
Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords再生不良性貧血 / トランスクリプトーム解析 / 造血不全 / 免疫学
Outline of Final Research Achievements

To identify aberrant molecular mechanisms involved in immune targeting of hematopoietic stem cells in bone marrow, we applied RNA-seq to examine the transcriptome of T cell subsets from AA/PNH patients and healthy control subjects. Differentially expressed gene analysis in four different T cell subsets from PNH and healthy control subjects showed distinct transcriptional profiles, depending on the T cell subsets. By pathway analysis, we identified novel signaling pathways in T cell subsets, including increased gene expression involved in TNFR, IGF1, NOTCH, AP-1, and ATF2 pathways. Dysregulation of several candidate genes (JUN, TNFAIP3, TOB1, GIMAP4, GIMAP6, TRMT112, NR4A2, CD69, and TNFSF8) was validated by quantitative real-time RT-PCR and flow cytometry.

Academic Significance and Societal Importance of the Research Achievements

骨髄不全型PNHにおいてT細胞を正または負に制御するパスウェイや遺伝子が同定されたことから、これらの遺伝子を標的とした治療への応用が期待される。

Report

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

    (10 results)

All 2019 2018 2017

All Journal Article (4 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 4 results,  Open Access: 1 results) Presentation (5 results) (of which Int'l Joint Research: 4 results,  Invited: 1 results) Book (1 results)

  • [Journal Article] Escape hematopoiesis by HLA-B5401-lacking hematopoietic stem progenitor cells in men with acquired aplastic anemia.2019

    • Author(s)
      Mahmoud I. Elbadry、Mizumaki Hiroki、Hosokawa Kohei、J. Luis Espinoza、Nakagawa Noriharu、Chonabayashi Kazuhisa、Yoshida Yoshinori、Katagiri Takamasa、Hosomichi Kazuyoshi、Zaimoku Yoshitaka、Imi Tatsuya、Mai Anh Thi Nguyen、Fujii Youichi、Tajima Atsushi、Ogawa Seishi、Takenaka Katsuto、Akashi Koichi、Nakao Shinji
    • Journal Title

      Haematologica

      Volume: 印刷中 Issue: 10 Pages: 210856-210856

    • DOI

      10.3324/haematol.2018.210856

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Establishment of a flow cytometry assay for detecting paroxysmal nocturnal hemoglobinuria-type cells specific to patients with bone marrow failure2018

    • Author(s)
      Hosokawa Kohei、Sugimori Chiharu、Ishiyama Ken、Takamatsu Hiroyuki、Noji Hideyoshi、Shichishima Tsutomu、Obara Naoshi、Chiba Shigeru、Ninomiya Haruhiko、Shirasugi Yukari、Nakamura Yoshihiko、Ando Kiyoshi、Ueda Yasutaka、Yonemura Yuji、Kawaguchi Tatsuya、Nishimura Jun-ichi、Kanakura Yuzuru、Nakao Shinji
    • Journal Title

      Annals of Hematology

      Volume: 97 Issue: 12 Pages: 2289-2297

    • DOI

      10.1007/s00277-018-3443-1

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Abnormal RNA splicing and genomic instability after induction of DNMT3A mutations by CRISPR/Cas9 gene editing2018

    • Author(s)
      Banaszak LG, Giudice V, Zhao X, Wu Z, Gao S, Hosokawa K, Keyvanfar K, Townsley DM, Gutierrez-Rodrigues F, Fernandez Ibanez MDP, Kajigaya S, Young NS
    • Journal Title

      Blood cells, molecules & diseases

      Volume: 69 Pages: 10-22

    • DOI

      10.1016/j.bcmd.2017.12.002

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] T Cell Transcriptomes from Paroxysmal Nocturnal Hemoglobinuria Patients Reveal Novel Signaling Pathways.2017

    • Author(s)
      Hosokawa K, Kajigaya S, Keyvanfar K, Qiao W, Xie Y, Townsley DM, Feng X, Young NS.
    • Journal Title

      The Journal of Immunology

      Volume: 199(2) Issue: 2 Pages: 477-488

    • DOI

      10.4049/jimmunol.1601299

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 免疫性造血不全における変異造血幹細胞によるエスケープ造血2018

    • Author(s)
      細川晃平、中尾眞二
    • Organizer
      第80回 日本血液学会学会学術集会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Escape Hematopoiesis By HLA-B5401-Lacking Hematopoietic Stem Progenitor Cells in Male Patients with Acquired Aplastic Anemia2018

    • Author(s)
      Kohei Hosokawa, Mahmoud Ibrahim Elbadry, Hiroki Mizumaki, Luis Espinoza, Noriharu Nakagawa, Kazuhisa Chonabayashi, Yoshinori Yoshida, Takamasa Katagiri, Yoshitaka Zaimoku, Tatsuya Imi, Nguyen Thi Mai Anh, Yoichi Fujii, Seishi Ogawa, Katsuto Takenaka, Koichi Akashi and Shinji Nakao
    • Organizer
      2018 ASH annual meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Bystander Proliferation of Piga-Mutated Hematopoietic Progenitor Cells in Acquired Aplastic Anemia Patients Possessing HLA Class I Allele-Lacking Leukocytes2018

    • Author(s)
      Takeshi Yoroidaka, Kohei Hosokawa, Tatsuya Imi, Takamasa Katagiri, Fumihiro Azuma and Shinji Nakao
    • Organizer
      2018 ASH annual meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Loss-of-Function Mutations in HLA-Class I Alleles in Acquire Aplastic Anemia: Evidence for the Involvement of Limited Class I Alleles in the Auto-Antigen Presentation of Aplastic Anemia2018

    • Author(s)
      Hiroki Mizumaki, Kazuyoshi Hosomichi, Tanabe Mikoto, Takeshi Yoroidaka, Tatsuya Imi, Yoshitaka Zaimoku, Kohei Hosokawa, Takamasa Katagiri, Hiroyuki Takamatsu, Tatsuhiko Ozawa, Fumihiro Azuma, Hiroyuki Kishi, Atsushi Tajima and Shinji Nakao
    • Organizer
      2018 ASH annual meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The Depletion of TGF-β Co-Receptor CD109 Induces Erythroid Differentiation of TF-1 Cells: A Model of Preferential Commitment of PIGA-Mutated Hematopoietic Stem Cells in Immune-Mediated Bone Marrow Failure2018

    • Author(s)
      Tanabe Mikoto, Noriharu Nakagawa, Kohei Hosokawa, Luis Espinoza, Kana Maruyama, Takamasa Katagiri, Hirohito Yamazaki and Shinji Nakao
    • Organizer
      2018 ASH annual meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Book] Congenital and Acquired Bone Marrow Failure2017

    • Author(s)
      Hosokawa K, Scheinberg P, and Young, N.S.
    • Total Pages
      274
    • Publisher
      Elsevier
    • ISBN
      9780128041529
    • Related Report
      2017 Research-status Report

URL: 

Published: 2017-04-28   Modified: 2020-03-30  

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