LncRNA JPX contributes to Treg/Th17 imbalance in allergic rhinitis <i>via</i> targeting the miR-378g/CCL5 axis

Aim: T-regulatory (Treg)/T-helper (Th) 17 imbalance contributes to the pathogenesis of allergic rhinitis (AR). Long non-coding RNAs (lncRNAs) participate in the progression of AR. Herein, the effect of lncRNA JP X on Treg/Th17 balance in AR was explored. Methods: CD4+ T cells were isolated from patients with AR and healthy control. The percentage of Treg and Th17 cells were examined by flow cytometry. The levels of JP X, miR-378g, CCL5, T GF-β, and IL-17A were tested using qRT-P CR. The protein expression of Foxp3 and RORγt was measured by western blot. Results: The data showed that an imbalance of Treg/Th17 was associated with AR. Upregulation of JP X was found in AR, and knockdown of which improved the imbalance of Treg/Th17. Furthermore, JP X functioned as a sponge of miR-378g to upregulate CCL5. Inhibition of miR-378g reversed the effects on Treg/Th17 induced by silencing of JP X. Moreover, overexpression of CCL5 reversed miR-378g-induced effects. Conclusion: In conclusion, depletion of JP X promoted Treg/Th17 balance in AR via regulating the miR-378g/CCL5 axis. The findings provided a novel therapeutic insight for AR.</p

Frequencies of the haplotypes formed by rs17375018, rs7517847, rs1343151 and rs11209032 SNPs in AR patients and healthy control individuals.

<p>AR, allergic rhinitis; OR, odds ratio.</p

Frequencies of alleles and genotypes of IL-23R polymorphisms in AR patients and control individuals.

<p>AR, allergic rhinitis; OR, odds ratio; SNP, single-nucleotide polymorphism.</p><p>Logistic regression analysis was used to analyze the genotype allele controlling for age, gender and occupation as the covariables.</p

The 4 SNP call rates in patients and control individuals and HWE p-values.

<p>AR, allergic rhinitis, SNP; single-nucleotide polymorphism; HWE,Hardy-Weinberg equilibrium.</p

Clinical features and demographic characteristics of the study population.

<p>AR, allergic rhinitis.</p

CRSsNP and CRSwNP are two distinct disease entities with respect to remodeling patterns.

<p>The hypothesis was supported by the significantly higher protein concentrations of activin A, follistatin, TGF-β1, and IFNγ and the lower concentrations of IL-5 and ECP, lower ratios of follistatin/activinA in CRSsNP compared with CRSwNP tissue homogenates, in line with predominant fibrosis in CRSsNP and edema in CRSwNP.</p

Protein expression of ECP, IL-5 and IFNγ in nasal tissue from CRSsNP (n = 13), CRSwNP (n = 23) and Control patients (inferior turbinate) (n = 10).

<p>IFNγ protein expression was significantly higher and IL-5 and ECP expression was significantly lower in CRSsNP compared with CRSwNP. Significance is indicated by P value.</p

The ratios of Follistatin/ActivinA and Follistatin/TGF-beta1 in nasal tissue and supernatants.

<p>There was an imbalance between pro-fibrotic (TGF-beta1, activin A) and anti-fibrotic (follistatin) mediators in CRSsNP (n = 9) and CRSwNP (n = 7). Statistical analysis was performed by using the Wilcoxon test (for paired comparisons). Significance is indicated by P value.</p

Patient’s details.

<p># p = 0.0097 (CRSwNP vs Control) was obtained by ANOVA. Constituent ratio was compared by crosstabs. Gender comparison was done by Chi-square test</p><p>*Fisher exact test. P <0. 05 was considered statistically significant.</p><p>Patient’s details.</p

Spontaneous release of activin A (A), Follistatin (B) and TGF-beta1 (C) in supernatants of nasal tissue fragments from CRSsNP (n = 9) and CRSwNP patients (n = 7).

<p>The release of activin A (p = 0.015) (Fig 3A) and follistatin (p = 0.005) (Fig 3B) was higher in CRSwNP than in CRSsNP subjects; in contrast, the release of TGF-β1 (p = 0.036) (Fig 3C) was lower in CRSwNP than in CRSsNP at 24h. *<i>P</i><0.05 compared to 1h and 4h.</p