Elucidating the Pathogenesis of Autoimmune Pituitary Disease Using Human iPS Cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08555
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Kobe University
• Principal Investigator: Iguchi Genzo 神戸大学, インクルーシブキャンパス&ヘルスケアセンター, 教授 (60346260)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 自己免疫性下垂体疾患 / iPS細胞 / 抗PIT-1下垂体炎

Outline of Final Research Achievements

In this study, we successfully cloned specific CTLs from the peripheral blood of patients with autoimmune pituitary disease and determined specific TCR, antigens, and HLA. By co-culturing these specific CTLs with pituitary cells derived from the patients' iPS cells, we successfully reproduced the pathology of anti-PIT-1 pituitary inflammation. This disease-specific in vitro reconstitution model is the first of its kind as a model of human autoimmune disease. This model enables the exploration of previously unexplored areas that were challenging in existing research, allowing for the elucidation of disease mechanisms using a human cell model that did not exist before. Furthermore, using this disease model, we successfully identified new molecular pathways and established a screening system for drug treatments that inhibit cellular damage.

Free Research Field

代謝・内分泌

Academic Significance and Societal Importance of the Research Achievements

本研究で用いた手法を用いることで、他の自己免疫性下垂体疾患や細胞性免疫関連自己免疫疾患の解析にも広く応用できる。これにより、詳細な発症メカニズムの解明や新薬の開発に貢献する可能性がある。さらに、本研究で確立した疾患モデルは重要であり、申請者が発見した自己免疫性下垂体疾患（抗PIT-1下垂体炎）は、自己免疫疾患としてだけでなく腫瘍随伴症候群としての側面も持つため、両疾患の発症メカニズムの解析に非常に有用である。今後、安全で効果的な自己免疫疾患および癌の治療法の開発に繋がることが期待される。