Role of TREM-1 signaling by PGLYRP1/PGN in inflammatory diseases

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K16654
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49050:Bacteriology-related
• Research Institution: Tokyo University of Agriculture
• Principal Investigator: Hosoda Hiroshi 東京農業大学, 生命科学部, 准教授 (40408662)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: TREM-1 / Ligand / PGLYRP1

Outline of Final Research Achievements

TREM-1 acts as a membrane receptor on innate immune cells to enhance inflammatory cytokine production and exacerbate the pathogenesis of sepsis, as well as an enhancer of various non-infectious chronic inflammatory diseases. The peptidoglycan (PGN) recognition protein PGLYRP1 was reported to act as a PGN and TREM-1 ligand for the fungus, but the mechanism of this function was unknown. Therefore, we generated reporter cells for TREM-1 receptor signaling in macrophage-based cells and analyzed the role of TREM-1 signaling with PGLYRP1/PGN as a ligand. TREM-1 signaling was activated by commercially available PGLYRP1 and PGNs, but no effect on TREM-1 signaling was observed when using PGNs created by us.

Free Research Field

細菌学(含真菌学)

Academic Significance and Societal Importance of the Research Achievements

TREM-1の活性化により腫瘍の縮小が見られるなどTREM-1シグナリングと慢性炎症や腫瘍形成の関係に注目が集まっている。今回マウスマクロファージ系細胞株のJ774.1細胞をベースにTREM-1シグナル下流のNFATの活性化をモニターするLuciferaseレポーター細胞を作成し研究に用いた。PGLYRP1/PGNによるTREM-1の活性化について自作のPGNでは調査できなかったものの、細胞内Ca2+シグナルの惹起やTREM-1抗体により活性化されることが示されたことから、TREM-1シグナルのモニター、TREM-1シグナルを増強・減弱する分子のスクリーニングに利用できると考えられる。