Mechanisms of disruption of homeostasis in GVHD

2015 Fiscal Year Final Research Report

• Project/Area Number: 25293217
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Hokkaido University
• Principal Investigator: Teshima Takanori 北海道大学, 医学(系)研究科(研究院), 教授 (40284096)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 造血幹細胞移植 / ＧＶＨＤ / 腸幹細胞 / パネート細胞 / R-Spondin1 / defensin

Outline of Final Research Achievements

We studied on target tissue injury in graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation and found that intestinal stem cells and their niche are targeted by alloreactive donor T cells. Intestinal ecology system is also distiubed and such a disruption of tissue homeostasis of intestinal microbial ecology is associated with clinical manifestation of GVHD. We found that Intestinal stem cell growth factor R-spondin1 promotes growth of both intestinal stem cells and Paneth cells. Brief administration of R-spondin1 to hosts protects the intestinal stem-niche system, ameliorates GVHD, prevents infection, and improves transplant outcome. Our study suggests that such novel strategies to maintain host homeostasis could improve transplant outcome.

Free Research Field

血液内科学