MicroRNAs regulate immune system via multiple targets.

MicroRNAs (miRNAs) represent the most abundant class of regulators of gene expression. Each miRNA may suppress multiple mRNA targets, while one mRNA can be targeted by many miRNAs for precise control of a wide range of cellular processes. The important role of miRNAs in the immune system is highlighted by the conditional Dicer knockout mouse, which exhibited profound aberrant development and function of immune cells. One particular miRNA, miR-155, is highly expressed and plays important role in lymphocytes. In this review we focused on the role of miRNA, especially miR-155, via their predicted and known mRNA targets in innate and adaptive immunity. Finally, we discussed the potential of miRNAs as novel targets for the diagnosis and therapy of immune system diseases.

Up-regulation of microRNA-210 induces immune dysfunction via targeting FOXP3 in CD4(+) T cells of psoriasis vulgaris.

Psoriasis vulgaris (PV) is a chronic inflammatory and T cell-mediated autoimmune skin disease. An immune dysfunction that is manifested by abnormally activated T cells and defective regulatory T (Treg) cells may play an important role in the pathogenesis of PV. However, the precise mechanism of the immune dysfunction in PV patients still remains unclear. In this study, we found that miR-210 expression is increased significantly in CD4(+) T cells from patients with PV and confirmed that FOXP3 is a target gene of miR-210. We also found that overexpression of miR-210 inhibits FOXP3 expression and impairs the immunosuppressive functions of Treg cells in CD4(+) T cells from healthy controls. In contrast, inhibition of miR-210 increases FOXP3 expression and reverses the immune dysfunction in CD4(+) T cells from patients with PV. Our data demonstrates that increased miR-210 induces immune dysfunction via by FOXP3 in CD4(+) T cells from patients with PV.

Whole-genome DNA methylation in skin lesions from patients with psoriasis vulgaris.

Psoriasis, a chronic inflammatory skin disorder, is characterized by aberrant keratinocyte proliferation and differentiation in the epidermis. Although the pathogenesis of psoriasis is still incompletely understood, both genetic susceptibilities and environmental triggers are known to act as key players in its development. Several studies have suggested that DNA methylation is involved in the pathogenesis of psoriasis. However, the precise mechanisms underlying the regulation and maintenance of the methylome as well as their relationship with this disease remain poorly characterized. Herein, we used methylated DNA immunoprecipitation sequencing (MeDIP-Seq) to characterize whole-genome DNA methylation patterns in involved and uninvolved skin lesions from patients with psoriasis. The results of our MeDIP-Seq analyses identified differentially methylated regions (DMRs) covering almost the entire genome with sufficient depth and high resolution, showing that the number of hypermethylated DMRs was considerably higher than that of hypomethylated DMRs in involved psoriatic skin samples. Moreover, gene ontology analysis of MeDIP-Seq data showed that the aberrantly methylated genes belonged to several different ontological domains, such as the immune system, cell cycle and apoptosis. The results of the bisulfite-sequencing experiments for the genes PDCD5 and TIMP2 confirmed the methylation status identified by MeDIP-Seq, and the mRNA expression levels of these two genes were consistent with their DNA methylation profiles. To our knowledge, the present study constitutes the first report on MeDIP-Seq in psoriasis. The identification of whole-genome DNA methylation patterns associated with psoriasis provides new insight into the pathogenesis of this complex disease and represents a promising avenue through which to investigate novel therapeutic approaches.