Eosinophil differentiation in the bone marrow is promoted by protein tyrosine phosphatase SHP2

L. X. Xia, W. Hua, Y. Jin, B. P. Tian, Z. W. Qiu, C. Zhang, L. Q. Che, H. B. Zhou, Y. F. Wu, H. Q. Huang, F. Lan, Y. H. Ke, J. J. Lee, W. Li, S. M. Ying, Z. H. Chen, H. H. Shen

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

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 languageEnglish (US)
Article numbere2175
JournalCell Death and Disease
Volume7
DOIs
StatePublished - Apr 7 2016

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

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