Inhibitory mechanisms of neutrophilic inflammation induced by the activation of dopamine D2 receptor

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09920
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57030:Conservative dentistry-related
• Research Institution: Saitama Medical University
• Principal Investigator: Takagi Rie 埼玉医科大学, 医学部, 助手 (00569080)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ドーパミン(DA, dopamine) / 好中球性炎症 / ドーパミンD１様受容体 / ドーパミンD2様受容体 / Th17

Outline of Final Research Achievements

When dopamine acts on antigen presentation, it induces Th2, from immature CD4+ T cells, which protects against parasitic infection, and Th17, which protects against extracellular bacterial invasion, leading to the development of allergic diseases and neutrophilic inflammation (including autoimmune diseases). Dopamine D1-like receptor (D1R) antagonists act on this pathway to suppress Th2 and Th17 responses and improve the pathology of neutrophilic inflammation. Since dopamine D1R antagonists induce relative activation of dopamine D2-like receptors (D2R), it has been suggested that activation of dopamine D2R is involved in the improvement, but the details remain unknown. In this study, we focused on dopamine D2R and analyzed the mechanism for the suppression of neutrophilic inflammation by dopamine D2R activation.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

好中球性炎症を主体とする疾患は多く、自己免疫性好中球性炎症(多発性硬化症、1型糖尿病、自己免疫性腎炎)、非自己免疫性好中球性炎症(歯周病、化膿性アトピー性皮膚炎、好中球性気道炎症、子宮内膜症、副鼻腔炎、ニキビ) などに大別される。好酸球性炎症の特効薬として副腎皮質ステロイドがある一方で好中球性炎症に対する安価な特効薬は未だに知られていない。本研究では好中球性炎症モデルとして、歯周病のラットモデルを扱った。歯周病はヒトにおける感染症の中で最も有病率が高く脳梗塞や心筋梗塞に加え認知症などの発症リスクを上昇させる。その効果的な予防薬・治療薬の開発に研究成果を繋げる事に社会的意義を見出した。