miR-223: A Key Regulator in the Innate Immune Response in Asthma and COPD

Abstract

Asthma and Chronic Obstructive Pulmonary Disease (COPD) are chronic obstructive respiratory diseases characterized by airway obstruction, inflammation, and remodeling. Recent findings indicate the importance of microRNAs (miRNAs) in the regulation of pathological processes involved in both diseases. MiRNAs have been implicated in a wide array of biological processes, such as inflammation, cell proliferation, differentiation, and death. MiR-223 is one of the miRNAs that is thought to play a role in obstructive lung disease as altered expression levels have been observed in both asthma and COPD. MiR-223 is a hematopoietic cell-derived miRNA that plays a role in regulation of monocyte-macrophage differentiation, neutrophil recruitment, and pro-inflammatory responses and that can be transferred to non-myeloid cells via extracellular vesicles or lipoproteins. In this translational review, we highlight the role of miR-223 in obstructive respiratory diseases, focusing on expression data in clinical samples of asthma and COPD, in vivo experiments in mouse models and in vitro functional studies. Furthermore, we provide an overview of the mechanisms by which miR-223 regulates gene expression. We specifically focus on immune cell development and activation and involvement in immune responses, which are important in asthma and COPD. Collectively, this review demonstrates the importance of miR-223 in obstructive respiratory diseases and explores its therapeutic potential in the pathogenesis of asthma and COPD.

Keywords: COPD; asthma; inflammation; miR-223; miRNAs.

Figure 1

Overview of validated targets of miR-223. This overview illustrates all validated targets genes of miR-223 that could contribute to the pathogenesis of asthma and COPD. There were no studies that investigated validated targets of miR-223 in T-cells and eosinophils. The red cross indicates that miR-223 targets this gene and/or protein. CCL3, Chemokine (C-C motif) ligand 3; CUL1, cullin 1; CDK2, Cyclin-dependent kinase 2; CFTR, cystic fibrosis transmembrane conductance regulator; CXCL2, Chemokine (C-X-C motif) ligand 2; EPB41L3, erythrocyte membrane protein band 4.1 like 3; HDAC2, histone deacetylase 2; ICAM-1, Intercellular adhesion molecule 1; IGF-1R, insulin-like growth factor-1 receptor; IKKα, IκB kinase α; IL-6, Interleukin-6; Mef2c, Myocyte Enhancer Factor 2C; NLRP3, NOD-, LRR- and pyrin domain-containing protein 3; PARP-1, Poly [ADP-ribose] polymerase 1; RhoB, Rho-related GTP binding protein; STAT3, Signal transducer and activator of transcription 3; TAB2, TGF-Beta Activated Kinase 1 (MAP3K7) Binding Protein 2; TGFBR3, Transforming growth factor beta receptor III.