Mechanisms for the creation of neo-self in the thymus

2021 Fiscal Year Final Research Report

• Project Area: Creation, function and structure of neo-self
• Project/Area Number: 16H06496
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The University of Tokushima
• Principal Investigator: MATSUMOTO Mitsuru 徳島大学, 先端酵素学研究所, 教授 (60221595)
• Co-Investigator(Kenkyū-buntansha): 吉開 泰信 九州大学, 生体防御医学研究所, 学術研究員 (90158402)
• Project Period (FY): 2016-06-30 – 2021-03-31
• Keywords: 胸腺 / 自己免疫疾患 / Aire / innate T細胞 / ネオ・セルフ

Outline of Final Research Achievements

Aire, a transcriptional regulator whose defect results in the development of autoimmunity, controls the transcriptome of medullary thymic epithelial cells (mTECs) including the genes for self-antigens. Mechanisms for this process, however, remained incompletely understood. our results uncover multilayered transcriptional control by Aire in mTECs with revealing two distinct classes of gene regulation. On the other hand, γδ T cells producing IL-17A (γδTh17 cells) are known to be involved in peritonitis induced by Escherichia coli infection in mice. In vivo treatment with Vγ6-specific mAb (1C10-1F7) significantly hampered resolution of E. coli infection. Thus, Vγ6+ γδTh17 cells mainly contributed to protection against E. coli infection.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

その機能障害や過剰および異所性発現により、実際にヒトやマウスに病気がもたらされることから、Aireの研究によって自己免疫疾患においても「真の実験医学」が可能になったと言える。他方、IL-17A産生γδ型T細胞は子宮頸部粘膜下層、大腸の粘膜固有層、腹腔、肺、皮膚真皮に多く存在し、大腸菌と肺炎桿菌の感染早期の防御に働くことを示した。さらに、乾癬モデルおよび褥瘡モデルを用いて好中球を誘導し、innate T細胞が皮膚炎症の誘導を担うことも明らかにした。以上の知見は、自己免疫疾患の発症阻止ならびに生体防御機構における胸腺の役割を明らかにしたものであり、その社会的意義は大きい。