2021 Fiscal Year Final Research Report

Inflammation cellular society in pulmonary fibrosis

Planned Research

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Project Area	Preventive medicine through inflammation cellular sociology
Project/Area Number	17H06392
Research Category	Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
Allocation Type	Single-year Grants
Review Section	Complex systems
Research Institution	Tokyo University of Science (2018-2021) The University of Tokyo (2017)
Principal Investigator	Matsushima Kouji 東京理科大学, 研究推進機構生命医科学研究所, 教授 (50222427)
Co-Investigator(Kenkyū-buntansha)	橋本真一和歌山県立医科大学, 先端医学研究所, 教授 (00313099) 上羽悟史東京理科大学, 研究推進機構生命医科学研究所, 准教授 (00447385) 伊藤利洋奈良県立医科大学, 医学部, 教授 (00595712) 七野成之東京理科大学, 研究推進機構生命医科学研究所, 助教 (70822435)
Project Period (FY)	2017-06-30 – 2022-03-31
Keywords	肺線維症 / single-cell RNA-seq / ネットワーク解析
Outline of Final Research Achievements	The objective of this project was to identify new preventive targets of pulmonary fibrosis by identifying molecules and cell subsets involved in the transition and regulation of the "inflammatory cell society," which is composed of the interaction of various cell types. We developed a novel scRNA-seq analysis method, TAS-Seq, which is much more sensitive and accurate than existing technologies, and identified C1q as a specific molecule for interstitial macrophages, which increase with the progression of silica-induced pulmonary fibrosis, and found that C1q directly affects fibroblasts and alveolar epithelial cells to promote fibrosis. Furthermore, we have constructed a temporal network model of the transition of inflammatory cell society based on temporal scRNA-seq data, and have identified and are validating the transition of hub cells and multiple secreting factors derived from them.
Free Research Field	炎症・免疫学
Academic Significance and Societal Importance of the Research Achievements	本研究により、肺線維症における炎症細胞社会の変遷の実態が解明され、その変遷に関与する新たな細胞集団や分子が同定された。また、炎症細胞社会のscRNA-seqデータに基づくモデル化手法を開発し、病態に関与しうる細胞や分子群が複数同定されている。さらに、それら解析の技術基盤として、高精度・高感度なscRNA-seq法TAS-Seqを開発した。これらの研究成果は、肺線維症におけるあたらな予防標的を提供するのみならず、その他様々な炎症病態解析に応用可能であるという点で、学術的意義は大きい。肺線維症の予防標的の同定は、COVID-19の感染拡大を踏まえると、社会的意義も大きいといえる。