ヤマト マサユキ   YAMATO Masayuki
  大和 雅之
   所属   研究施設 研究施設
   職種   教授
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 Integrin αvβ3 enhances the suppressive effect of interferon-γ on hematopoietic stem cells.
掲載誌名 正式名:The EMBO journal
略  称:EMBO J
ISSNコード:(1460-2075)0261-4189(Linking)
掲載区分国外
出版社 Transparent process
巻・号・頁 36(16),2390-2403頁
著者・共著者 UMEMOTO Terumasa†, MATSUZAKI Yu, SHIRATSCHI Yoshiko, HASHIMOTO Michihiro, YOSHIMOTO Takayuki, NAKAMURA-ISHIZU Ayako, PETRICH Brian, YAMATO Masayuki, SUDA Toshio*
発行年月 2017/07
概要 Hematopoietic homeostasis depends on the maintenance of hematopoietic stem cells (HSCs), which are regulated within a specialized bone marrow (BM) niche. When HSC sense external stimuli, their adhesion status may be critical for determining HSC cell fate. The cell surface molecule, integrin αvβ3, is activated through HSC adhesion to extracellular matrix and niche cells. Integrin β3 signaling maintains HSCs within the niche. Here, we showed the synergistic negative regulation of the pro-inflammatory cytokine interferon-γ (IFNγ) and β3 integrin signaling in murine HSC function by a novel definitive phenotyping of HSCs. Integrin αvβ3 suppressed HSC function in the presence of IFNγ and impaired integrin β3 signaling mitigated IFNγ-dependent negative action on HSCs. During IFNγ stimulation, integrin β3 signaling enhanced STAT1-mediated gene expression via serine phosphorylation. These findings show that integrin β3 signaling intensifies the suppressive effect of IFNγ on HSCs, which indicates that cell adhesion via integrin αvβ3 within the BM niche acts as a context-dependent signal modulator to regulate the HSC function under both steady-state and inflammatory conditions.
DOI 10.15252/embj.201796771
PMID 28673932