Fundamental research to establish novel therapies for sepsis targeting neutrophils

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16577
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55060:Emergency medicine-related
• Research Institution: Tohoku Medical and Pharmaceutical University
• Principal Investigator: Takai Jun 東北医科薬科大学, 医学部, 助教 (90813890)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 好中球 / ヒスタミン

Outline of Final Research Achievements

Sepsis is a multi-organ failure caused by infection-based systemic inflammation.
Recently, neutrophil extracellular traps have been reported to exacerbate sepsis by inducing inflammation. Meanwhile, we found that neutrophils can be divided into two distinct populations: histamine-producing and normal neutrophils. However, whether histamine-producing neutrophils are involved in the pathogenesis of sepsis remains largely unexplored.
In this study, we examined gene expression patterns of histamine-producing neutrophils and pathological analysis in a murine model of sepsis. We found that histamine-producing neutrophils showed higher gene expression levels related to allergy and inflammation. These results suggest that histamine-producing neutrophils induce inflammation during sepsis.

Free Research Field

医化学

Academic Significance and Societal Importance of the Research Achievements

これまで好中球は単一の細胞系列と考えられてきたが、本研究や他のグループの研究から、リンパ球やマクロファージのようにサブタイプが存在することが報告されている。したがって、ヒスタミン高産生好中球が敗血症病態の増悪に寄与することをさらに詳細な実験で示すことで、過剰な炎症を誘導する好中球のみを除去して通常好中球を残存させることで、生体防御能を維持させしながら炎症状態を改善させする新規治療法の分子基盤を確立できると考える。