Uncovering a novel therapeutic target for BMT-induced inflammation

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K23837
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0803:Pathology, infection/immunology, and related fields
• Research Institution: Hokkaido University
• Principal Investigator: Yoo Ji-Seung 北海道大学, 医学研究院, 助教 (30843437)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: GVHD / MHC class I / NLRC5 / Molecular target / Therapeutics

Outline of Final Research Achievements

Graft-versus-host disease (GVHD) is an unfavorable side effect of the allo-HSCT and a major limitation for the treatment of leukemia patients. However, currently, there are no effective medications available. The goal of my project was 1) to understand the underlying mechanism of the development of GVHD, 2) identify a molecular target involved in the disease onset, and 3) develop a novel therapeutic approach. During 2 years, I focused on the MHC class I pathway that is critically associated with disease onset and pathogenesis and achieved my research goals. I clarified that NLRC5, a master transactivator of the MHC class I pathway plays a critical role in the GVHD pathogenesis. Depletion of NLRC5 genes using the mouse model showed improved clinical outcomes. These findings will provide a novel idea for the development of GVHD therapeutics.

Free Research Field

Immunology. Inflammatory and iInfectious disease.

Academic Significance and Societal Importance of the Research Achievements

Organ transplantation recipients develop severe GVHD. However, current treatments are limited with strong side effects. More importantly, those drugs do not fundamentally cure the disease. My study contributes to the current science field and society by providing a novel therapeutic target for GVHD.