Analysis of thymic antigen presenting cells regulated by Aire in the negative selection

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08840
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: The University of Tokushima
• Principal Investigator: MOURI Yasuhiro 徳島大学, 大学院医歯薬学研究部(医学域), 助教 (80464353)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: Aire / 負の選択 / 胸腺髄質上皮細胞

Outline of Final Research Achievements

The regulation mechanism of negative selection by Aire remains elusive. Especially it is important which type of antigen presenting cells (APCs), medullary thymic epithelial cells (mTECs) or bone marrow (BM)-derived cells, are regulated by Aire in the negative selection. We have approached these issues by generating two different types of transgenic mouse (Tg) model, which express a prefixed model self-antigen driven by the insulin promoter or the Aire promoter. In the insulin-promoter Tg model, imaging analysis showed the dispensable role of Aire in cognate interaction between mTECs and autoreactive T cells. In the Aire-promoter Tg model, both mTECs and BM-derived APCs could independently induce clonal deletion. And production of Tregs by BM-derived APCs, which express and present the self-antigen, was impaired by the lack of Aire in mTECs, but not in BM-derived APCs. These results suggest that Aire regulates antigen presenting processes in BM-derived APCs rather than mTECs.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

胸腺における自己反応性T細胞の除去過程のメカニズムに関する理解は、自己免疫疾患の発生過程や病態形成を知る上で重要である。我々はこの過程においてAireがどのような抗原提示細胞を制御しているかに焦点を当てて研究を行った。これらの結果は胸腺における自己反応性T細胞の除去過程の学術的な知見にとどまらず、ヒトAIRE欠損症の発生メカニズムを理解する上で重要な知見であると思われる。