Functional analysis and its aplication on lung-resident memory Th17 cells

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K18385
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology; Bacteriology (including mycology)
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: KEIGO UENO 国立感染症研究所, 真菌部, 主任研究官 (10550220)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: クリプトコックス症 / メモリーT細胞 / 好中球 / ワクチン

Outline of Final Research Achievements

The pathogenic fungus Cryptococcus gattii infects healthy individuals. No vaccine is commercially available, and the protective immunity against this fungus has remained unclear. We have developed a dendritic cell (DC) vaccine and reported new memory T cells, lung-resident memory Th17 cells (Lung TRM17) induced by the DC vaccine. We reported that LungTRM17 is probably maintained in the lung independently of tertiary lymphoid tissues, and upon reinfection, it suppresses the progression of infection with the induction of neutrophils and multinucleated giant cells (Mucosal Immunol, 2018). Subsequently, we clarified the differentiation mechanism of neutrophils and the bactericidal mechanism against C. gattii (Sci Rep, 2018: Med Mycol, 2019), and also reported the mechanism by which C. gattii evades these immune recognitions (Eur J Immunol, 2021). Applying these findings, a new intranasal vaccine was successfully developed (64th Annual Meeting of the Japanese Society for Medical Mycology).

Free Research Field

真菌学, 免疫学

Academic Significance and Societal Importance of the Research Achievements

これまで長寿命性記憶型Th17細胞は報告がなかった。一方で、本研究はLung TRM17の感染防御作用や分化機構を解明し、これまでにない重要な知見を発信した。この研究を契機に、新しいワクチン抗原の開発にも成功し (PLOS ONE, 2019)、新規経鼻ワクチンの開発に繋がった。この経鼻ワクチンは、樹状細胞の養子移入に頼らずに、肺常在性記憶型T細胞を誘導することができ、第一世代のDCワクチンよりも強力に感染を抑制できる。この特徴は、肺常在性記憶型T細胞の研究ツールとして、より簡便に利用できることを意味しており、臨床応用可能な実践的なワクチンとしての性能も兼ね備えていることを意味している。