Elucidation of immunological memory of inflammatory T helper cells

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K19553
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Pathology, Infection/Immunology, and related fields
• Research Institution: Kyoto University
• Principal Investigator: Hirota Keiji 京都大学, ウイルス・再生医科学研究所, 准教授 (90631250)
• Project Period (FY): 2017-06-30 – 2020-03-31
• Keywords: T helper cells / IL-17 / Autoimmune disease

Outline of Final Research Achievements

In this study, we sought to elucidate the immunological memory formation, and maintenance of autoimmune T cells and a role of memory T cells in the exacerbation of autoimmune diseases. We have established a new reporter system capable of analyzing and separating the interleukin-17 (IL-17)-producing inflammatory T helper (Th17) cell lineage, and found that memory Th17 cells up-regulated pathogenic inflammatory cytokines and induced autoimmune arthritis. We also clarified the tissue distribution between memory Th17 cells and effector Th17 cells, specific differences in cell phenotype and function, and plasticity, and found a novel pathway of effector Th17 cells with disease-causing ability.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

自己免疫疾患の病勢が制御されている状態からの増悪、再発メカニズムに関しては不明な点が多く、メモリーTh17細胞の関与も含めた免疫学的分子基盤の解明が待たれています。本研究では、メモリーTh17細胞とエフェクターTh17細胞間の細胞生物学、免疫病理学的な特徴の理解が深まり、これまでのエフェクターTh17細胞を標的とした治療戦略だけではなく、その新しい供給源でもあるメモリーTh17細胞を同時に操作する免疫学的な治療法の開発が必要であることが強く示唆されました。