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2014 Fiscal Year Research-status Report

胸腺内Aire非依存的な末梢抗原の発現機構の解明

Research Project

Project/Area Number 26670231
Research InstitutionThe University of Tokyo

Principal Investigator

高場 啓之  東京大学, 医学(系)研究科(研究院), 研究員 (50637444)

Project Period (FY) 2014-04-01 – 2017-03-31
Keywords自己寛容
Outline of Annual Research Achievements

Immune tolerance or self/non-self discrimination has long been the fundamental issue in the field of immunology, for it is crucial for preventing autoimmune diseases. An autoimmune regulator, known as Aire, is expressed in medullary thymic epithelium cells (mTECs) and plays an essential role in the establishment of immune tolerance. Aire induces certain tissue-restricted antigen (TRA) genes in the thymus to eliminate autoreactive T cells. However, it has been known that many other TRAs are expressed independently of Aire, suggesting parallel independent pathway for the presentation of self-antigens. Therefore we investigated whether there is a hitherto unknown factor that functions as a regulator of autoimmunity by controlling TRA expression. Here we report the identification of a transcriptional regulator, which is required for the establishment of central tolerance by independently of Aire.

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

Not really any problems.

Strategy for Future Research Activity

We demonstrate that the novel transcriptional regulator controls a subset of TRA genes, the gene-deficient mice leads to autoimmune disorders, and the establishment of immune tolerance is supported by independently of Aire. Hence, we have identified a critical molecular player for the establishment of central tolerance as well as providing a novel therapeutic axis for the modulation of immune responses in the treatment of autoimmune diseases. It remains for future studies to determine whether the gene is related to autoimmune diseases in humans and associated with mTEC development and thymic Treg generation.

  • Research Products

    (1 results)

All 2015

All Presentation (1 results)

  • [Presentation] Identification of a novel key regulator of immune tolerance2015

    • Author(s)
      Hiroyuki Takaba and Hiroshi Takayanagi
    • Organizer
      Keystone symposia, T Cells: Regulation and Effector Function (oral presentation)
    • Place of Presentation
      Snowbird, Utah, USA
    • Year and Date
      2015-03-29 – 2015-04-03

URL: 

Published: 2016-05-27  

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