Identification of compound Y as an inhibitor of GPCR signaling regulator X

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16690
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: Osaka University
• Principal Investigator: Akiko Nakai 大阪大学, 免疫学フロンティア研究センター, 助教 (80768862)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 免疫学 / GPCR / ケモカイン受容体 / 炎症性疾患 / 細胞遊走

Outline of Final Research Achievements

Recently, we showed that GPCR signaling regulator X positively control B lymphocyte migration mediated by chemokine receptors and promotes humoral immune responses. Here, we identified compound Y as a compound that inhibits the functions of regulator X and reduces immune responses. Treatment with compound Y suppressed humoral immune responses and blocked arthritis progression in a mouse model of rheumatoid arthritis. These immunosuppressive effects of compound Y were abolished in mice expressing mutated regulator X that has an amino acid substitution at the binding position of compound Y. These findings suggest that compound Y inhibits immune responses by targeting regulator X.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

化合物YはGPCRのシグナル伝達の新規制御因子Xの機能を阻害することで液性免疫応答を抑制し、炎症性疾患の病態を改善することが明らかになった。本研究によって、化合物Yの抗炎症作用の新たな作用機序と共に、制御因子Xが過剰な免疫応答によって引き起こされる炎症性疾患治療の新たな創薬のターゲットになり得ることが示された。