Eosinophil differentiation in the bone marrow is promoted by protein tyrosine phosphatase SHP2.
Cell Death Dis
; 7: e2175, 2016 Apr 07.
Article
en En
| MEDLINE
| ID: mdl-27054330
ABSTRACT
SHP2 participates in multiple signaling events by mediating T-cell development and function, and regulates cytokine-dependent granulopoiesis. To explore whether and how SHP2 can regulate bone-marrow eosinophil differentiation, we investigate the contribution of SHP2 in the bone-marrow eosinophil development in allergic mice. Blockade of SHP2 function by SHP2 inhibitor PHPS-1 or conditional shp2 knockdown by adenovirus-inhibited bone-marrow-derived eosinophil differentiation in vitro, with no detectable effects on the apoptosis of eosinophils. Furthermore, SHP2 induced eosinophil differentiation via regulation of the extracellular signal-regulated kinase pathway. Myeloid shp2 conditional knockout mice (LysM(cre)shp2(flox/flox)) failed to induce eosinophilia as well as airway hyper-responsiveness. The SHP2 inhibitor PHPS-1 also alleviated eosinophilic airway inflammation and airway hyper-responsiveness, accompanied by significantly reduced levels of systemic eosinophils and eosinophil lineage-committed progenitors in allergic mice. We demonstrate that inhibition of eosinophil development is SHP2-dependent and SHP2 is sufficient to promote eosinophil formation in vivo. Our data reveal SHP2 as a critical regulator of eosinophil differentiation, and inhibition of SHP2 specifically in myeloid cells alleviates allergic airway inflammation.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Células de la Médula Ósea
/
Diferenciación Celular
/
Eosinófilos
/
Proteína Tirosina Fosfatasa no Receptora Tipo 11
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Idioma:
En
Revista:
Cell Death Dis
Año:
2016
Tipo del documento:
Article
País de afiliación:
China