Τρίτη 5 Απριλίου 2016

Increased microRNA-323-3p in IL-22/IL-17-producing T cells and asthma: a role in the regulation of the TGF-β pathway and IL-22 production

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Abstract

Background

IL-22- and IL-17-producing T cells have important roles in allergic diseases. microRNAs (miRNAs) are post-transcriptional regulators of gene expression and modulate numerous biological processes. Little is known about the functions of miRNAs in IL-22/IL-17-producing T cells.

Material and Methods

IL-22- and IL-17-positive T cells were sorted from human peripheral blood mononuclear cells (PBMCs) by intracellular staining and dual secretion assay. miRNA expression profiles were detected with TaqMan array microfluidic cards. T cells were transfected with miRNA mimics. Gene expression was analyzed using RT-qPCR and/or enzyme-linked immunosorbent assay in T cell subsets and PBMCs from patients with asthma and atopic dermatitis.

Results

The increased expression of miR-323-3p and non-coding RNA nc886 and reduced expression of miR-93, miR-181a, miR-26a and miR-874 were detected in IL-22-producing T cells. The pathway analysis of the putative targets suggested that these differentially expressed miRNAs could impact the proliferation, differentiation and effector functions of T cells. Further analyses showed the highest expression for miR-323-3p in IL-22- and IL-17-double-positive T cells and its capacity to suppress multiple genes from the transforming growth factor β pathway and the production of IL-22 in T cells. An increased expression of miR-323-3p in PBMCs from asthma patients and reverse correlation between miR-323-3p levels and IL-22 production in PBMCs cultured in T cell growth conditions was observed.

Conclusions

Our data suggest that miR-323-3p acts in a negative feedback loop to control the production of IL-22 in IL-22/IL-17-producing T cells and might thus impact the T cell responses in asthma.

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