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.
| Original language | English (US) |
|---|---|
| Article number | e2175 |
| Journal | Cell Death and Disease |
| Volume | 7 |
| DOIs | |
| State | Published - Apr 7 2016 |
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ASJC Scopus subject areas
- Cell Biology
- Immunology
- Cancer Research
- Cellular and Molecular Neuroscience
Cite this
Eosinophil differentiation in the bone marrow is promoted by protein tyrosine phosphatase SHP2. / Xia, L. X.; Hua, W.; Jin, Y.; Tian, B. P.; Qiu, Z. W.; Zhang, C.; Che, L. Q.; Zhou, H. B.; Wu, Y. F.; Huang, H. Q.; Lan, F.; Ke, Y. H.; Lee, J. J.; Li, W.; Ying, S. M.; Chen, Z. H.; Shen, H. H.
In: Cell Death and Disease, Vol. 7, e2175, 07.04.2016.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Eosinophil differentiation in the bone marrow is promoted by protein tyrosine phosphatase SHP2
AU - Xia, L. X.
AU - Hua, W.
AU - Jin, Y.
AU - Tian, B. P.
AU - Qiu, Z. W.
AU - Zhang, C.
AU - Che, L. Q.
AU - Zhou, H. B.
AU - Wu, Y. F.
AU - Huang, H. Q.
AU - Lan, F.
AU - Ke, Y. H.
AU - Lee, J. J.
AU - Li, W.
AU - Ying, S. M.
AU - Chen, Z. H.
AU - Shen, H. H.
PY - 2016/4/7
Y1 - 2016/4/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84963627694&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84963627694&partnerID=8YFLogxK
U2 - 10.1038/cddis.2016.74
DO - 10.1038/cddis.2016.74
M3 - Article
C2 - 27054330
AN - SCOPUS:84963627694
VL - 7
JO - Cell Death and Disease
JF - Cell Death and Disease
SN - 2041-4889
M1 - e2175
ER -