Regulatory effect of microRNA-135a on the Th1/Th2 imbalance in a murine model of allergic rhinitis.

Yanyun Luo,Yu Xu,Yuqin Deng,Jibo Han,Zezhang Tao,Yonggang Kong,Zhe Chen,Bokui Xiao,Shiming Chen,Jie Ren,Minjie Deng

doi:10.3892/etm.2014.1855

Abstract

Allergic rhinitis (AR) is primarily caused by a T helper cell (Th)1/Th2 imbalance. In a murine AR model of a previous study, the serum ovalbumin (OVA)-sIgE concentration was high, whereas microRNA (miR)-135a was lowly expressed in the nasal mucosa. The abnormal expression pattern of miR-135a coincided with highly expressed endogenous factors, including GATA binding protein (GATA)-3 and interleukin (IL)-4, and lowly expressed factors, including T-box expressed in T cells (T-bet) and interferon (IFN)-γ. We hypothesized that miR-135a may play an important role in immune regulation in AR mice. In the present study, AR was induced by OVA in the mice. Two groups of the AR mice were treated with a miR-135a mimic and a mimic control, respectively. The serum and nasal mucosa were collected for analysis. Following miR-135a application, the serum OVA-sIgE concentration was significantly reduced. In the nasal mucosa, the expression levels of miR-135a were higher, the mRNA and protein expression levels of GATA-3 and IL-4 were lower, and the expression levels of T-bet and IFN-γ were higher. The miR-135a corrected the Th1/Th2 imbalance in the AR mice. Findings of this study may provide a basis for novel genetic treatments in addressing allergic diseases.

Highlights

Allergic rhinitis (AR) is a common disease that affects the quality of life and induces other risk factors, including asthma, termed as ‘one airway, one disease’
The mRNA expression levels of T‐box expressed in T cells (T‐bet) and IFN‐γ were significantly reduced and those of GATA‐3 and IL‐4 were significantly increased in the AR mice compared with those in the control group (Fig. 2)
It was found that the targets of the miR‐135a 3' UTR included the 3' UTR of GATA‐3

Summary

Introduction

Allergic rhinitis (AR) is a common disease that affects the quality of life and induces other risk factors, including asthma, termed as ‘one airway, one disease’. MicroRNAs (miRNAs or miRs) are a class of small molecule RNAs, which play an important role in the regulation of gene expression at the post‐transcriptional level [16]. MiR‐126 upregulates the expression levels of the gene POU domain class 2 associating factor 1 This gives rise to high expression levels of the transcription factor PU. and low expression levels of GATA‐3, thereby inhibiting the secretion of the Th2 cytokines, IL‐4, IL‐5 and IL‐13, in the airway of an asthma mouse model and relieving the airway allergic inflammatory reaction [23]. Lack of miR‐155 led to the enhancement of its target transcription factor c‐Maf, causing favorable differentiation of Th0 cells into Th2 cells, with enhanced production levels of LUO et al: miR-135a AFFECTS Th1/Th2 IMBALANCE the Th2 cytokine, IL‐4 [34]. Repression of miR‐155 expression increased the expression levels of another target, IFN‐γ receptor α chain (Rα), suggesting that IFN‐γRα inhibited the response of Th1 cells to the antiproliferative effects of IFN‐γ [37]

Methods

Results

Conclusion