title: MiR-223 deficiency increases eosinophil progenitor proliferation.
abstract: 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.
authors: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
authors: Thomas X
authors: TX
authors: Lu
authors: Eun-Jin
authors: EJ
authors: Lim
authors: John A
authors: JA
authors: Besse
authors: Svetlana
authors: S
authors: Itskovich
authors: Andrew J
authors: AJ
authors: Plassard
authors: Patricia C
authors: PC
authors: Fulkerson
authors: Bruce J
authors: BJ
authors: Aronow
authors: Marc E
authors: ME
authors: Rothenberg
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D015536:Down-Regulation / Q000276:immunology; D004804:Eosinophils / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology*
chemical_list: C544877:MIRN223 microRNA, mouse; D035683:MicroRNAs