Integrin ?v?3 enhances the suppressive effect of interferon-? on hematopoietic stem cells.

ABSTRACT: 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 ?v?3, is activated through HSC adhesion to extracellular matrix and niche cells. Integrin ?3 signaling maintains HSCs within the niche. Here, we showed the synergistic negative regulation of the pro-inflammatory cytokine interferon-? (IFN?) and ?3 integrin signaling in murine HSC function by a novel definitive phenotyping of HSCs. Integrin ?v?3 suppressed HSC function in the presence of IFN? and impaired integrin ?3 signaling mitigated IFN?-dependent negative action on HSCs. During IFN? stimulation, integrin ?3 signaling enhanced STAT1-mediated gene expression via serine phosphorylation. These findings show that integrin ?3 signaling intensifies the suppressive effect of IFN? on HSCs, which indicates that cell adhesion via integrin ?v?3 within the BM niche acts as a context-dependent signal modulator to regulate the HSC function under both steady-state and inflammatory conditions.

SUBMITTER: Umemoto T 

PROVIDER: S-EPMC5556268 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature