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Role of NR4A2 in pathogenic Th cells in autoimmune diseases

Research Project

Project/Area Number 17K16135
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Neurology
Research InstitutionNational Center of Neurology and Psychiatry

Principal Investigator

Raveney Ben  国立研究開発法人国立精神・神経医療研究センター, 神経研究所 免疫研究部, 科研費研究員 (70795385)

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: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsImmunology / Autoimmune diseases / T cells / Th17 / Autoimmunity / Multiple Sclerosis
Outline of Final Research Achievements

The autoimmune disease multiple sclerosis (MS) occurs when immune cells enter the brain and spine, become activated, and cause damage to self-tissues, leading to peripheral and neurological disabilities. Previously, we found that a particular gene, called NR4A2, was increased in immune cells in the blood of MS patients. In this study, we investigated how this NR4A2 gene was involved in the activation of T helper cells, a type of immune cells strongly associated with damage in MS disease, although currently the nature of these T cells that cause disease is hotly debated.
Our results showed that NR4A2 controls the type of response that T helper cells make during the initiation of autoimmune disease whey they become activated in brain/spine tissues. In particular, we discovered that NR4A2 determines if T helper cells become a pathogenic cells type, which cause damage in MS-like diseases and that these damage-associated T cells expressed novel features the allow targeting for treatment.

Academic Significance and Societal Importance of the Research Achievements

This study provides new information about features of authentic damage-associated T cells in autoimmune disease. This will aid future study of the process these cells are involved in and increase understanding of cellular immunology in diseased tissues as well as providing new targets for treatment.

Report

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

    (11 results)

All 2018 2017

All Presentation (11 results) (of which Int'l Joint Research: 5 results,  Invited: 4 results)

  • [Presentation] Characterization of novel Eomes-positive cytotoxic T helper cells in chronic autoimmune CNS inflammation2018

    • Author(s)
      Ben JE Raveney
    • Organizer
      FOCIS 2018, San Francisco, USA
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Increases in Eomes-expressing Th cells in secondary progressive multiple sclerosis reveal patients at risk of increased disability2018

    • Author(s)
      Ben JE Raveney
    • Organizer
      ISNI, Brisbane, Australia
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Eomes+ Th cells: biomarker for SPMS disease status2018

    • Author(s)
      Ben JE Raveney
    • Organizer
      JSNI, Fukushima, Japan
    • Related Report
      2018 Annual Research Report
  • [Presentation] Level of Eomes+ Th cells predicts worsening disease in secondary progressive multiple sclerosis2018

    • Author(s)
      Ben JE Raveney
    • Organizer
      JSI, Fukuoka
    • Related Report
      2018 Annual Research Report
  • [Presentation] Worsening symptoms in secondary progressive multiple sclerosis are linked to increased eomes+ Th cells2018

    • Author(s)
      Ben JE Raveney
    • Organizer
      ECTRIMS, Berlin, Germany
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Identification of novel pathogenic factors in acute and chronic autoimmune disease2017

    • Author(s)
      Ben J Raveney
    • Organizer
      Closed meeting, Department of Clinical Neurology, University of Nottingham, Nottingham, UK
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] NR4A2 and Eomes: novel pathogenic factors in acute and chronic autoimmune neuroinflammation2017

    • Author(s)
      Ben J Raveney
    • Organizer
      Joint meeting Division of Immunology and Department of Ophthalmology, University of Bristol, Bristol, UK
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Eomes-positive cytotoxic T helper cells: a new pathogenic player in secondary progressive multiple sclerosis?2017

    • Author(s)
      Ben J Raveney
    • Organizer
      Workshop on Biomarkers in Neuropsychaiatric Disorders, Max Planck Institute of Psychiatry, Munich, Germany
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Eomes-expressing T helper cells as a target for secondary progressive MS2017

    • Author(s)
      Ben J Raveney
    • Organizer
      JMSS Annual meeting, Tokyo, Japan
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Characterization of novel Eomes-positive cytotoxic T helper cells in chronic autoimmune CNS inflammation2017

    • Author(s)
      Raveney, B.J.E., Lin, Y., Sato, W., Oki, S., Yamamura, T.
    • Organizer
      British Society for Immunology Annual Congress, Brighton, UK
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Eomes-positive cytotoxic T helper cells: a new pathogenic immune cell subset in secondary progressive multiple sclerosis?2017

    • Author(s)
      Raveney, B.J.E., Sato, W., Oki, S., Yamamura, T.
    • Organizer
      Japanese Society for Immunology Annual Meeting, Sendai, Japan
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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

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