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.
Highlights
Generally classified into two main types: M1 and M2 macrophages
Alternative activation of macrophages is induced by a broader range of stimuli including interleukin 4 (IL-4), interleukin 13 (IL-13), interleukin 10 (IL-10), or glucocorticoids, and alternative macrophages are specialized in defense against extracellular pathogens, promoting tissue repair and the resolution of the inflammatory process [2]
MiR-155 Directly Targets IL-13 receptor ␣1 chain (IL13R␣1)—By performing bioinformatic analysis, we found that IL13R␣1 has two putative binding sites for miR-155 in the 3Ј-UTR, and it was predicted to be a direct target for miR-155 (Fig. 1)
Summary
Generally classified into two main types: M1 (classically activated) and M2 (alternatively activated) macrophages. Alternative activation of macrophages is induced by a broader range of stimuli including interleukin 4 (IL-4), interleukin 13 (IL-13), interleukin 10 (IL-10), or glucocorticoids, and alternative macrophages are specialized in defense against extracellular pathogens, promoting tissue repair and the resolution of the inflammatory process [2] Regardless of this classification, one of the most remarkable characteristics of macrophages is their plasticity and heterogeneity, depending on the specific task carried out. Once bound to the receptor, STAT6 is phosphorylated by JAKs, which causes its activation, dimerization, and translocation to the nucleus, where it exerts its transcriptional roles [13] Since their relatively recent discovery [14], miRNAs have been shown to play important biological roles in different contexts: during development, cell differentiation, and immune regulation and in pathologies such as cancer [15,16,17]. It is well established that miR-155 plays a central role in the development of a healthy immune system and as a pro-Th1 microRNA
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
