The molecular basis of tissue inflammation mediated by Th17 cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 19H01026
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Medium-sized Section 49:Pathology, infection/immunology, and related fields
• Research Institution: Kyoto University
• Principal Investigator: Hirota Keiji 京都大学, 医生物学研究所, 准教授 (90631250)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: Th17細胞 / 自己免疫疾患 / 炎症性疾患 / IL-17 / IL-23

Outline of Final Research Achievements

In this research project, we analyzed the differentiation mechanism of inflammatory T helper (Th17) cells that produce the inflammatory cytokine interleukin-17, and the mechanism of inflammation aggravation due to interaction with other inflammation-related cells.
We identified the characteristics of Th17 cells that are highly pathogenic in the arthritic joints. We also revealed the mechanism by which interleukin-23-producing cells, which strongly regulate the function of Th17 cells, acquire functions in the gut. We elucidated that Gsdmd and Ripk3 are not involved as factors that exacerbate and aggravate inflammation, and on the other hand, we found the role of CCR2+ inflammatory monocytes that aggravate synovial inflammation.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、自己免疫疾患を起こす炎症性T細胞がどのように分化し機能するかを明らかにした。また、炎症性T細胞を強くコントロールするサイトカインIL-23を産生する樹状細胞が腸管組織でどのように機能を獲得するのかを明らかにした。自己免疫疾患での標的臓器で炎症を増幅させる細胞間相互作用の役割についても明らかにした。これらの分子機構や細胞を標的とすることで、将来的に、治療法開発に結びつくことが期待できる。