miR-223 Deficiency Increases Eosinophil Progenitor Proliferation

Recently, microRNAs have been shown to be involved in hematopoietic cell development, but their role in eosinophilopoiesis has not yet been described. In this article, we show that miR-223 is upregulated during eosinophil differentiation in an ex vivo bone marrow–derived eosinophil culture system. Targeted ablation of miR-223 leads to an increased proliferation of eosinophil progenitors. We found upregulation of a miR-223 target gene, IGF1R, in the eosinophil progenitor cultures derived from miR-223−/− mice compared with miR-223+/+ littermate controls. The increased proliferation of miR-223−/− eosinophil progenitors was reversed by treatment with an IGF1R inhibitor (picropodophyllin). Whole-genome microarray analysis of differentially regulated genes between miR-223+/+ and miR-223−/− eosinophil progenitor cultures identified a specific enrichment in genes that regulate hematologic cell development. Indeed, miR-223−/− eosinophil progenitors had a delay in differentiation. Our results demonstrate that microRNAs regulate the development of eosinophils by influencing eosinophil progenitor growth and differentiation and identify a contributory role for miR-223 in this process.

[1]  C. Lam,et al.  MicroRNA-21* regulates the prosurvival effect of GM-CSF on human eosinophils. , 2013, Immunobiology.

[2]  J. Hernández-Rivas,et al.  Response to imatinib mesylate in patients with hypereosinophilic syndrome , 2012, International Journal of Hematology.

[3]  A. Brodsky,et al.  MicroRNA Profiling in Mucosal Biopsies of Eosinophilic Esophagitis Patients Pre and Post Treatment with Steroids and Relationship with mRNA Targets , 2012, PloS one.

[4]  D. Yee Insulin-like growth factor receptor inhibitors: baby or the bathwater? , 2012, Journal of the National Cancer Institute.

[5]  Lisa J. Martin,et al.  MicroRNA signature in patients with eosinophilic esophagitis, reversibility with glucocorticoids, and assessment as disease biomarkers. , 2012, The Journal of allergy and clinical immunology.

[6]  Yong Li,et al.  Chinese Anti鄄 Cancer a Ssociation , 2022 .

[7]  M. Rothenberg,et al.  Epigenetic Regulation of the IL-13-induced Human Eotaxin-3 Gene by CREB-binding Protein-mediated Histone 3 Acetylation* , 2011, The Journal of Biological Chemistry.

[8]  P. Geurts,et al.  MicroRNAs Profiling in Murine Models of Acute and Chronic Asthma: A Relationship with mRNAs Targets , 2011, PloS one.

[9]  F. Finkelman,et al.  Advances in mechanisms of asthma, allergy, and immunology in 2010. , 2011, The Journal of allergy and clinical immunology.

[10]  J. Stenvang,et al.  MiR-155 is overexpressed in patients with atopic dermatitis and modulates T-cell proliferative responses by targeting cytotoxic T lymphocyte-associated antigen 4. , 2010, The Journal of allergy and clinical immunology.

[11]  Allen D. Delaney,et al.  Comprehensive microRNA expression profiling of the hematopoietic hierarchy , 2010, Proceedings of the National Academy of Sciences.

[12]  Terry J. Smith Insulin-Like Growth Factor-I Regulation of Immune Function: A Potential Therapeutic Target in Autoimmune Diseases? , 2010, Pharmacological Reviews.

[13]  J. Lieberman,et al.  Small RNAs Guide Hematopoietic Cell Differentiation and Function , 2010, The Journal of Immunology.

[14]  Bruce J. Aronow,et al.  ToppCluster: a multiple gene list feature analyzer for comparative enrichment clustering and network-based dissection of biological systems , 2010, Nucleic Acids Res..

[15]  P. Venge The eosinophil and airway remodelling in asthma , 2010, The clinical respiratory journal.

[16]  O. Larsson,et al.  Targeting the insulin-like growth factor-1 receptor by picropodophyllin as a treatment option for glioblastoma. , 2010, Neuro-oncology.

[17]  S. Phipps,et al.  Antagonism of microRNA-126 suppresses the effector function of TH2 cells and the development of allergic airways disease , 2009, Proceedings of the National Academy of Sciences.

[18]  Jing Chen,et al.  ToppGene Suite for gene list enrichment analysis and candidate gene prioritization , 2009, Nucleic Acids Res..

[19]  Marc E. Rothenberg,et al.  MicroRNA-21 Is Up-Regulated in Allergic Airway Inflammation and Regulates IL-12p35 Expression 1 , 2009, The Journal of Immunology.

[20]  D. Broide,et al.  Advances in mechanisms of asthma, allergy, and immunology in 2008. , 2009, The Journal of allergy and clinical immunology.

[21]  S. Siegel,et al.  Functionally Competent Eosinophils Differentiated Ex Vivo in High Purity from Normal Mouse Bone Marrow1 , 2008, The Journal of Immunology.

[22]  S. Phipps,et al.  Eosinophils: Biological Properties and Role in Health and Disease , 2008, Clinical and Experimental Allergy.

[23]  O. Larsson,et al.  Picropodophyllin induces downregulation of the insulin-like growth factor 1 receptor: potential mechanistic involvement of Mdm2 and β-arrestin1 , 2008, Oncogene.

[24]  O. Kirak,et al.  Regulation of progenitor cell proliferation and granulocyte function by microRNA-223 , 2008, Nature.

[25]  Robert M. Anthony,et al.  Protective immune mechanisms in helminth infection , 2007, Nature Reviews Immunology.

[26]  Yoko Fukuda,et al.  An Evolutionarily Conserved Mechanism for MicroRNA-223 Expression Revealed by MicroRNA Gene Profiling , 2007, Cell.

[27]  K. Akashi,et al.  Identification of eosinophil lineage–committed progenitors in the murine bone marrow , 2005, The Journal of experimental medicine.

[28]  J. Lammers,et al.  Differential regulation of granulopoiesis by the basic helix-loop-helix transcriptional inhibitors Id1 and Id2. , 2005, Blood.

[29]  A. Multani,et al.  Disruption of the NAD(P)H:quinone oxidoreductase 1 (NQO1) gene in mice causes myelogenous hyperplasia. , 2002, Cancer research.

[30]  Thomas D. Schmittgen,et al.  Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. , 2001, Methods.

[31]  D. Jones The eosinophil. , 1993, Journal of comparative pathology.