Mechanism of lung fibrosis in chronic GVHD

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H04879
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Juntendo University
• Principal Investigator: OHNUMA Kei 順天堂大学, 医学(系)研究科(研究院), 准教授 (10396872)
• Co-Investigator(Kenkyū-buntansha): 森本 幾夫 順天堂大学, 医学(系)研究科(研究院), 特任教授 (30119028) ; 岩尾 憲明 順天堂大学, 医学部, 准教授 (00309139) ; 岩田 哲史 順天堂大学, 医学(系)研究科(研究院), 非常勤講師 (00396871)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 慢性GVHD / CD26 / Caveolin-1 / IL-26 / 造血幹細胞移植

Outline of Final Research Achievements

Obliterative bronchiolitis (OB) is the only manifestation of pulmonary chronic GVHD (cGVHD). We identified a novel effect of IL-26 on cGVHD. Humanized cGVHD mice exhibited OB with increased collagen deposition and predominant infiltration with human IL-26CD26CD4T cells. IL-26 increased collagen synthesis in fibroblasts and that collagen contents were increased in a murine GVHD model using IL26 Tg mice. IA significant increase in IL-26 production by CD4T cells following CD26 costimulation, while immunoglobulin Fc domain fused with the N-terminal of caveolin-1, the ligand for CD26, (Cav-Ig) effectively inhibited production of IL-26. Administration of Cav-Ig before or after onset of GVHD impeded the development of cGVHD without interrupting engraftment of donor-derived human cells, with preservation of the GVL effect. We concluded that cGVHD of the lungs is caused in part by IL-26CD26CD4T cells, and that treatment with Cav-Ig could be beneficial for cGVHD prevention and therapy.

Free Research Field

医学