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Ruxolitinib protects skin stem cells and maintains skin homeostasis in murine graft-versus-host disease

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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
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)

Submitter: 橋本 大吾

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