mechanisms of vasculopathy in chronic GVHD

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K16309
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Jichi Medical University
• Principal Investigator: Morita Kaoru 自治医科大学, 医学部, 助教 (20813223)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: GVHD / GVL / endothelium

Outline of Final Research Achievements

Chronic GVHD (Graft-versus-Host Disease) is a systemic autoimmune-like complication that occurs after allogeneic transplantation, but the specific cells targeted within tissues are not well understood. This study revealed that vascular endothelial cells produce various chemokines and cytokines, which are biomarkers of chronic GVHD. These factors attract and activate immune cells locally. The production of these factors involves IFN-γ, and ROCK2 inhibitors were found to be effective in regulating this process. Furthermore, vascular endothelial cells express alloantigen/HLA class II complexes on their membranes, and some leukemia cells also exhibit these complexes. This suggests that vascular endothelial cells are involved not only in chronic GVHD but also in the Graft-versus-Leukemia (GVL) effect.

Free Research Field

GVHD

Academic Significance and Societal Importance of the Research Achievements

慢性GVHDは適切なマウスモデルがないこともあり、病態解明が十分に進んでいない。本研究によって、血管内皮細胞が慢性GVHDにおいて重要な役割を果たすことが明らかになったことで、疾患の病態生理学的メカニズムに新たな知見を提供できると考えている。また、IFN-γやROCK2阻害剤が慢性GVHDの制御に関与することが示され、今後、新たな治療戦略の開発につながる可能性がある。