| Title: | Ruxolitinib protects skin stem cells and maintains skin homeostasis in murine graft-versus-host disease |
| Authors: | Takahashi, Shuichiro Browse this author |
| Hashimoto, Daigo Browse this author →KAKEN DB |
| Hayase, Eiko Browse this author |
| Ogasawara, Reiki Browse this author |
| Ohigashi, Hiroyuki Browse this author |
| Ara, Takahide Browse this author |
| Yokoyama, Emi Browse this author |
| Ebata, Ko Browse this author |
| Matsuoka, Satomi Browse this author |
| Hill, Geoffrey R. Browse this author |
| Sugita, Junichi Browse this author |
| Onozawa, Masahiro Browse this author →KAKEN DB |
| Teshima, Takanori Browse this author →KAKEN DB |
| Issue Date: | 3-May-2018 |
| Publisher: | American Society of Hematology |
| Journal Title: | Blood |
| Volume: | 131 |
| Issue: | 18 |
| Start Page: | 2074 |
| End Page: | 2085 |
| Publisher DOI: | 10.1182/blood-2017-06-792614 |
| Abstract: | Graft-versus-host disease (GVHD) is the major complication after allogeneic stem cell transplantation (SCT). Emerging evidence indicates that GVHD leads to injury of intestinal stem cells. However, it remains to be investigated whether skin stem cells could be targeted in skin GVHD. Lgr5+ hair follicle stem cells (HFSCs) contribute to folliculogenesis and have a multipotent capacity to regenerate all epithelial cells in repair. We studied the fate of Lgr5+ HFSCs after SCT and explored the novel treatment to protect Lgr5+ HFSCs against GVHD using murine models of SCT. We found that GVHD reduced Lgr5+ HFSCs in association with impaired hair regeneration and wound healing in the skin after SCT. Topical corticosteroids, a standard of care for a wide range of skin disorders including GVHD, damaged HFSCs and failed to improve skin homeostasis, despite of their anti-inflammatory effects. In contrast, JAK1/2 inhibitor ruxolitinib significantly ameliorated skin GVHD, protected Lgr5+ HFSCs, and restored hair regeneration and wound healing after SCT. We, for the first time, found that GVHD targets Lgr5+ HFSCs and that topical ruxolitinib represents a novel strategy to protect skin stem cells and maintain skin homeostasis in GVHD. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/73806 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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