Long non-coding RNAs as the regulators and targets of macrophage M2 polarization

Macrophages are immune cells with high heterogeneity and plasticity. M2 polarization is one extreme of the well-established phenotypes of macrophage polarization, and involves in diverse biological processes. The polarization process is initiated at the command of numerous components. Long non-coding RNAs (lncRNAs) are RNAs longer than 200 nucleotides with limited protein-coding capacity. Recent studies have revealed a newly found subset of lncRNAs engaged in the M2 polarization and their potent and multifunctional roles in developing diseases. By interfering with specific signaling pathways and altering the active mode, acting as the sponges of microRNAs or decoys of transcription factors, lncRNAs prompted macrophages to an M2 phenotype. Further, lncRNAs can bind to the genome to regulate the chromatin dynamics or work as a platform for protein complexes tether. Exosomal lncRNAs can also orchestrate the polarization in a paracrine way. To make it easier to interpret the roles of lncRNAs in the M2 polarization, we review the reported lncRNAs according to the underlying mechanisms. Moreover, we discuss the possibilities of targeting macrophages' M2 polarization using the oligonucleotides drugs or clustered regularly interspaced palindromic repeats (CRISPR) technologies to provoke wisdom on the therapeutic strategies.