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

Takahashi, Shuichiro; Hashimoto, Daigo; Hayase, Eiko; Ogasawara, Reiki; Ohigashi, Hiroyuki; Ara, Takahide; Yokoyama, Emi; Ebata, Ko; Matsuoka, Satomi; Hill, Geoffrey R.; Sugita, Junichi; Onozawa, Masahiro; Teshima, Takanori

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

Takahashi, Shuichiro; Hashimoto, Daigo; Hayase, Eiko et al.

Blood, 2018, 131(18), 2074-2085

Permalink : https://hdl.handle.net/2115/73806

このアイテムのアクセス数:841件（2026-10-05 21:47 集計）

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論文情報

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アクセス権	open access
URI	https://hdl.handle.net/2115/73806
タイトル	Ruxolitinib protects skin stem cells and maintains skin homeostasis in murine graft-versus-host disease
著者	Takahashi, Shuichiro ; Hashimoto, Daigo ; Hayase, Eiko ; Ogasawara, Reiki ; Ohigashi, Hiroyuki ; Ara, Takahide ; Yokoyama, Emi ; Ebata, Ko ; Matsuoka, Satomi ; Hill, Geoffrey R. ; Sugita, Junichi ; Onozawa, Masahiro ; Teshima, Takanori
著者名 Takahashi, Shuichiro
e-Rad_Researcher 20419576 著者名 Hashimoto, Daigo
著者名 Hayase, Eiko
著者名 Ogasawara, Reiki
著者名 Ohigashi, Hiroyuki
著者名 Ara, Takahide
著者名 Yokoyama, Emi
著者名 Ebata, Ko
著者名 Matsuoka, Satomi
著者名 Hill, Geoffrey R.
著者名 Sugita, Junichi
e-Rad_Researcher 70455632 著者名 Onozawa, Masahiro
e-Rad_Researcher 40284096 著者名 Teshima, Takanori
言語	英語
発行日	2018-05-03
出版者	American Society of Hematology
収録物名	Blood
巻(号)	131(18)
ページ	2074-2085
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
PISSN	0006-4971
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.1182/blood-2017-06-792614