Analysis on the autoimmune hepatitis elicited in young PD-1 knockout mice

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02717
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Nara Institute of Science and Technology
• Principal Investigator: Ishida Yasumasa 奈良先端科学技術大学院大学, 先端科学技術研究科, 准教授 (10221756)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: PD-1 / Msh2 / ゲノム変異 / neoantigen / 自己免疫 / 肝炎

Outline of Final Research Achievements

In some cancer patients, antibody-mediated blockade of the PD-1 function leads to the cure of the disease. However, we still do not fully understand the physiological function(s) of PD-1 in healthy individuals without cancers. When we created two experimental systems in which accumulation of genome mutations is accelerated in mice without PD-1, we observed the development of autoimmune diseases in both of the systems. This observation strongly suggests that PD-1 suppresses immune reactions against mutated proteins originated from genome mutations.

Free Research Field

免疫病理学

Academic Significance and Societal Importance of the Research Achievements

がん患者の体内では、がん細胞中のゲノム変異に由来する「変異タンパク質」に対する免疫応答が、PD-1 によって抑制されてしまうことが明らかになっているが、なぜそのような「有益な」免疫応答が PD-1 によって抑制されなければならないのか？これまでは明らかでなかった。今回の研究により、その理由が解明された。