Development of fibrosis specific biomarker for graft-versus-host disease

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K17366
• 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: Hokkaido University
• Principal Investigator: Ohigashi Hiroyuki 北海道大学, 医学研究院, 助教 (20845284)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: HSP47 / transplantation

Outline of Final Research Achievements

Allogeneic hematopoietic stem cell transplantation is a curative treatment for hematologic malignancies, but graft-versus-host disease (GVHD) remains a serious complication. Previous studies have demonstrated that heat shock protein 47 (HSP47), a fibrosis-specific molecular chaperone, is highly expressed in a chronic GVHD model mouse and may serve as a therapeutic target. This study investigated whether serum HSP47 could be a biomarker for assessing the indication of antifibrotic therapy using a GVHD model mouse. Although the utility of HSP47 as a biomarker could not be demonstrated, it was revealed that TGF-β produced by macrophages infiltrating the liver injures the tissue stem cells of the bile duct epithelium and that transiently exhausted T cells are the responsible cells in chronic GVHD.

Free Research Field

hematopoietic cell transplantation

Academic Significance and Societal Importance of the Research Achievements

同種造血細胞移植は難治性造血器腫瘍への根治的治療法だが、移植片対宿主病(Graft-versus-Host disease; GVHD)は治療の成否や患者の長期のQOLに関わる重要な合併症である。本研究で線維化特異的バイオマーカーの開発には至らなかったが、急性GVHDの主要な標的臓器である肝臓GVHDの病態が明らかになることで、慢性GVHDへの移行が低下する可能性がある。また、一過性疲弊T細胞が慢性GVHDの責任細胞であることが明らかになったことで、新たなGVHD予防法の開発につながる可能性がある。