Dynamic control of immune and inflammatory cell behavios by peropheral nervous system

2024 Fiscal Year Final Research Report

• Project Area: Glia decoding: deciphering information critical for brain-body interactions
• Project/Area Number: 20H05901
• Research Category: Grant-in-Aid for Transformative Research Areas (A)
• Allocation Type: Single-year Grants
• Review Section: Transformative Research Areas, Section (III)
• Research Institution: Osaka University
• Principal Investigator: ISHII MASARU 大阪大学, 大学院生命機能研究科, 教授 (10324758)
• Project Period (FY): 2020-11-19 – 2025-03-31
• Keywords: 組織マクロファージ / 自律神経 / イメージング / シングルセル解析

Outline of Final Research Achievements

This study aimed to elucidate the molecular and cellular mechanisms of inflammation control in the liver using advanced techniques such as intravital multiphoton imaging, laser ablation, and spatiotemporal single-cell analysis. The researchers identified a novel anti-inflammatory macrophage (MP2) localized around the portal vein and clarified its molecular characteristics and dependence on gut microbiota. Furthermore, they discovered neuron-associated macrophages (pNAMs) closely linked to sympathetic nerves, which contribute to the construction of the periportal sympathetic nerve network and regulate vascular permeability and immune tolerance within the liver. These findings reveal the essence of liver-specific immune regulation and propose new therapeutic targets for liver diseases.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究は、肝臓に特有の炎症制御システムの実態を初めて細胞実体レベルで明らかにし、従来の臓器横断的理解を超える革新をもたらした点で学術的意義が大きい。特に、腸内細菌との相互作用による抗炎症マクロファージの誘導、神経と免疫系の密接な連関は、免疫学・神経科学・微生物学の学際的研究を加速させる。社会的には、慢性肝炎、脂肪肝炎、自己免疫性胆管炎といった難治性肝疾患の新規治療法開発に向けた重要な基盤知識を提供し、肝疾患患者のQOL向上や医療負担軽減への貢献が期待される。