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Identification of the selective immune system against human herpesvirus and novel therapies development

Research Project

Project/Area Number 17K17692
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Pediatrics
Virology
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Hoshino Akihiro  東京医科歯科大学, 大学院医歯学総合研究科, 非常勤講師 (80465137)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
KeywordsEpstein Barrウイルス / 水痘帯状疱疹ウイルス / 原発性免疫不全症 / ヒトヘルペスウイルス / 機能解析 / 免疫機構
Outline of Final Research Achievements

Primary immunodeficiencies (PIDs) are congenital disorders caused by monogenic germline mutations affecting the immune system. Germline mutations were identified in patients with severe Epstein-Barr virus (EBV) and/or varicella-zoster virus (VZV)-associated diseases. It is of interest not only to identify the PIDs as the underlying diseases, but also to determine how alterations affect immune system, providing further understanding of human immune system. In this research, we demonstrated 2 things: (1) EBV and VZV are recognized and induce T-cell activation through virus-specific pathway. (2) More than 10% of functional CD8+ T cells could modify the clinical presentations supported by the observations of reverted T cells in PID patients.

Academic Significance and Societal Importance of the Research Achievements

本研究は、ヒトへルペスウイルス(HHV)に起因する重症疾患の原因解明に加えて、将来的な治療法の発展に寄与する。原発性免疫不全症(PID)の一部では遺伝子治療あるいは養子免疫療法が将来的な治療法として期待されているが、SAP欠損症に対してはCD8+T細胞の10%以上を補正すればHHVの一つであるEpstein-Barr ウイルス(EBV)に対する制御が期待できることが示唆された。また、EBVは腫瘍ウイルスとしても知られており、それに対する免疫機構の解明は、基礎にPIDがないより多くの人口におけるEBV関連疾患の治療開発の基盤を確立することになる。

Report

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

    (15 results)

All 2020 2019 2018 Other

All Int'l Joint Research (1 results) Journal Article (12 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 11 results,  Open Access: 6 results) Presentation (2 results) (of which Int'l Joint Research: 1 results)

  • [Int'l Joint Research] INSERM(フランス)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Inherited chromosomally integrated human herpesvirus‐6 in a patient with XIAP deficiency2020

    • Author(s)
      Inoue Kento、Miura Hiroki、Hoshino Akihiro、Kamiya Takahiro、Tanita Kay、Ohye Tamae、Park Myoung‐Ja、Yanagimachi Masakatsu、Takagi Masatoshi、Imai Kohsuke、Morio Tomohiro、Yoshikawa Tetsushi、Kanegane Hirokazu
    • Journal Title

      Transplant Infectious Disease

      Volume: - Issue: 5

    • DOI

      10.1111/tid.13331

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] High-throughput analysis revealed the unique immunoglobulin gene rearrangements in plasmacytoma-like post-transplant lymphoproliferative disorder2020

    • Author(s)
      Hoshino A, Nishimura A, Naruto T, Okano T, Matsumoto K, Okamoto K, Shintaku H, Tokoro S, Okamoto H, Wada T, Takagi M, Imai K, Kanegane H, Morio T
    • Journal Title

      Br J Haematol

      Volume: - Issue: 4

    • DOI

      10.1111/bjh.16583

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Disseminated fusariosis in a child after haploidentical hematopoietic stem cell transplantation.2020

    • Author(s)
      Hoshino A, Tokoro S, Akashi T, Inoue M, Takagi M, Imai K, Kanegane H, Muraosa Y, Kamei K, Morio T
    • Journal Title

      Pediatr Int

      Volume: 62 Issue: 3 Pages: 419-420

    • DOI

      10.1111/ped.14097

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] An 18-Year-Old Male With X-linked Lymphoproliferative Syndrome Type 1 Who Developed Primary Central Nervous System Lymphoma 6 Months After Primary Epstein-Barr Virus Infection2019

    • Author(s)
      Kusano N, Sakata N, Sugimoto K, et al.
    • Journal Title

      J Pediatr Hematol Oncol

      Volume: 41 Issue: 8 Pages: e538-e541

    • DOI

      10.1097/mph.0000000000001424

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hematopoietic stem cell transplantation recovers insulin deficiency in type 1 diabetes mellitus associated with IPEX syndrome2019

    • Author(s)
      Yamauchi T, Takasawa K, Kamiya T, et al.
    • Journal Title

      Pediatr Diabetes

      Volume: 20 Issue: 7 Pages: 1035-1040

    • DOI

      10.1111/pedi.12895

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of autoantibodies using human proteome microarrays in patients with IPEX syndrome2019

    • Author(s)
      Hoshino Akihiro、Kanegane Hirokazu、Nishi Masanori、Tsuge Ikuya、Tokuda Kiriko、Kobayashi Ichiro、Imai Kohsuke、Morio Tomohiro、Takagi Masatoshi
    • Journal Title

      Clinical Immunology

      Volume: 203 Pages: 9-13

    • DOI

      10.1016/j.clim.2019.03.011

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epstein-Barr Virus-Associated γδ T-Cell Lymphoproliferative Disorder Associated With Hypomorphic IL2RG Mutation2019

    • Author(s)
      Tanita K, Hoshino A, Imadome K, Kamiya T, Inoue K, Okano T, Yeh TW, Yanagimachi M, Shiraishi A, Ishimura M, Schober T, Rohlfs M, Takagi M, Imai K, Takada H, Ohga S, Klein C, Morio T, Kanegane H.
    • Journal Title

      Front Pediatr

      Volume: 7 Pages: 15-15

    • DOI

      10.3389/fped.2019.00015

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Inherited lymphoproliferative disorders2019

    • Author(s)
      金兼 弘和、星野 顕宏
    • Journal Title

      Rinsho Ketsueki

      Volume: 60 Issue: 6 Pages: 708-715

    • DOI

      10.11406/rinketsu.60.708

    • NAID

      130007675231

    • ISSN
      0485-1439, 1882-0824
    • Related Report
      2019 Annual Research Report
  • [Journal Article] Modification of cellular and humoral immunity by somatically reverted T cells in X-linked lymphoproliferative syndrome type 12019

    • Author(s)
      Hoshino A, Yang X, Tanita K, Yoshida K, Ono T, Nishida N, Okuno Y, Kanzaki T, Goi K, Fujino H, Ohshima K, Shiraishi Y, Chiba K, Tanaka H, Miyano S, Ogawa S, Kojima S, Morio T, Kanegane H.
    • Journal Title

      J Allergy Clin Immunol

      Volume: 143 Issue: 1 Pages: 421-424

    • DOI

      10.1016/j.jaci.2018.07.044

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] High frequencies of asymptomatic Epstein-Barr virus viremia in affected and unaffected individuals with CTLA4 mutations.2018

    • Author(s)
      Hoshino A, Tanita K, Kanda K, Imadome K, Shikama Y, Yasumi T, Imai K, Takagi M, Morio T, Kanegane H.
    • Journal Title

      Clin Immunol

      Volume: 195 Pages: 45-48

    • DOI

      10.1016/j.clim.2018.07.012

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Dysregulation of Epstein-Barr virus infection in hypomorphic ZAP70 mutation.2018

    • Author(s)
      Hoshino A, Takashima T, Yoshida K, Morimoto A, Kawahara Y, Yeh TW, Okano T, Yamashita M, Mitsuiki N, Imai K, Sakatani T, Nakazawa A, Okuno Y, Shiraishi Y, Chiba K, Tanaka H, Miyano S, Ogawa S, Kojima S, Morio T, Kanegane H.
    • Journal Title

      J Infect Dis

      Volume: 印刷中

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Phenotype, penetrance, and treatment of 133 CTLA-4-insufficient individuals.2018

    • Author(s)
      Schwab C, Gabrysch A, Olbrich P, Patiño V, Warnatz K, Wolff D, Hoshino A, Kobayashi M, Imai K, Takagi M, Dybedal I, Haddock JA, Sansom D, Lucena JM, Seidl M, et al.
    • Journal Title

      J Allergy Clin Immunol

      Volume: 印刷中

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Plasmacytoma-like post-transplant lymphoproliferative disorder with multiple autoantibodies in a XIAP deficient patient.2019

    • Author(s)
      Hoshino A, Okano T, Matsumoto K, Nishimura A, Shintaku H, Tokoro S, Okamoto H, Wada T, Mitsuiki N, Kajiwara M, Takagi M, Imai K, Kanegane H, Morio T.
    • Organizer
      2019 Focused Meeting of the European Society for Immunodeficiencies
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] SAP欠損症(XLP1)におけるT細胞のリバータントによる免疫能の回復 -国内予後調査から-2018

    • Author(s)
      星野顕宏、Xi Yang、吉田健一、小野敏明、谷田けい、西田直徳、奥野友介、神崎健仁、合井久美子、大島孝一、白石友一、千葉健一、田中洋子、宮野悟、小川誠司、小島勢二、森尾友宏、金兼弘和
    • Organizer
      第27回EBV感染症研究会
    • Related Report
      2017 Research-status Report

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

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