title: The interleukin 13 (IL-13) pathway in human macrophages is modulated by microRNA-155 via direct targeting of interleukin 13 receptor alpha1 (IL13Ralpha1).
abstract: Macrophages play a central role in the balance and efficiency of the immune response and are at the interface between innate and adaptive immunity. Their phenotype is a delicate equilibrium between the M1 (classical, pro-Th(1)) and M2 (alternative, pro-Th(2)) profiles. This balance is regulated by cytokines such as interleukin 13 (IL-13), a typical pro-M2-Th(2) cytokine that has been related to allergic disease and asthma. IL-13 binds to IL-13 receptor α1 (IL13Rα1), a component of the Type II IL-4 receptor, and exerts its effects by activating the transcription factor signal transducer and activator of transcription 6 (STAT6) through phosphorylation. MicroRNAs are short (∼22 nucleotide) inhibitory non-coding RNAs that block the translation or promote the degradation of their specific mRNA targets. By bioinformatics analysis, we found that microRNA-155 (miR-155) is predicted to target IL13Rα1. This suggested that miR-155 might be involved in the regulation of the M1/M2 balance in macrophages by modulating IL-13 effects. miR-155 has been implicated in the development of a healthy immune system and function as well as in the inflammatory pro-Th(1)/M1 immune profile. Here we have shown that in human macrophages, miR-155 directly targets IL13Rα1 and reduces the levels of IL13Rα1 protein, leading to diminished activation of STAT6. Finally we also demonstrate that miR-155 affects the IL-13-dependent regulation of several genes (SOCS1, DC-SIGN, CCL18, CD23, and SERPINE) involved in the establishment of an M2/pro-Th(2) phenotype in macrophages. Our work shows a central role for miR-155 in determining the M2 phenotype in human macrophages.
authors.affiliation: JunkRNA Laboratory, Division of Infection, Inflammation and Immunity, University of Southampton School of Medicine, Southampton General Hospital, Southampton SO16 6YD, United Kingdom.
authors.forename: Rocio T
authors.initials: RT
authors.lastname: Martinez-Nunez
authors.forename: Fethi
authors.initials: F
authors.lastname: Louafi
authors.forename: Tilman
authors.initials: T
authors.lastname: Sanchez-Elsner
mesh_terms: D001249:Asthma / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D053661:Interleukin-13 Receptor alpha1 Subunit / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D035683:MicroRNAs / Q000276:immunology / Q000378:metabolism*; D010766:Phosphorylation / Q000235:genetics / Q000276:immunology; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: C508181:IL13RA1 protein, human; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human