| 研究実績の概要 |
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.
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| 今後の研究の推進方策 |
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.
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