| Background and Purposes:Allergic rhinitis(AR)is one of the most common noninfectious chronic upper respiratory diseases in the world,mainly based on Th2 type immune response.The clinical symptom repeatedly and seriously affects the life and work of the patient.What's more,AR is the basis of many complications and a major risk factor for poor asthma control.At present,the clinical treatment of AR is still mainly based on symptomatic treatment,such as intranasal steroids and antihistamines.The application of specific immunotherapy still limited.Therefore,it is necessary to investigate the genes responsible for the development and progression,and identify new prognostic biomarkers and therapeutic targets in AR.MicroRNAs(miRNAs)belong to a family of small noncoding single-stranded RNAs that involved in the regulation of posttranscriptional gene expression by binding to target mRNAs to promoting mRNA degradation or blocking protein translation.Mounting investigations implicate that miRNAs can affect allergic inflammation by regulating the function of immune cell.Among immune system-related miRNAs,miR-155 is the most closely related to immune regulation.Group 2 innate lymphoid cells(ILC2s)lack the surface expression of the common lineage markers associated with T cells,B cells,and other leukocytes but are capable of producing large amounts of type 2 cytokines(IL-4,IL-5,and IL-13)also shown to promote Th2-type inflammation.However,the mechanism of interaction between miR-155 and ILC2 in AR has not been investigated.Therefore,this study explored the role and mechanism of miR-155 in regulating the function of ILC2 in the pathogenesis of AR.The results will help to understand the pathogenesis of AR and find new molecular targets for establishing possible interventions.Methods:1.The nasal mucosa tissues and peripheral blood samples of 26 AR patients and 28 healthy controls were collected.The mRNA expression levels of miR-155,IL-25 and IL-33 in nasal mucosa tissues were determined using quantitative real time polymerase chain reaction(qRT-PCR).The frequency of ILC2 s in human peripheral blood was quantified by Flow cytometry analysis.Then analyze the correlation between miR-155 and ILC2.2.AR model was established in female Balb/C mice by intranasal challenges with recombinant murine IL-33.miR-155 agomir or antagomir was then intranasally administrated to mice,while the control group was treated with equal amount saline.The symptom of nasal rubbing and sneezing were recorded after the last challenge.Nasal mucosa tissues of each group were stained with hematoxylin and eosin(H&E)for histopathological examination.3.Nasal mucosa tissues and serum were collected.miR-155 expression and Th2 cytokines(IL-4,IL-5,IL-9 and IL-13)were measured by qRT-PCR,Enzyme-linked immunosorbent assay(ELISA)or western blotting,respectively.The frequency of ILC2 s in mice nasal mucosa was quantified by flow cytometry analysis.Results:1.Compared with healthy controls,the mRNA expression levels of miR-155(0.571 ± 0.068 vs 1.778 ± 0.247,P <0.001),IL-25(0.228 ± 0.069 vs 0.434 ± 0.048,p <0.05)and IL-33(2.013 ± 0.781 vs 30.480 ± 5.782,p <0.001)were increased in nasal mucosa tissues of AR patients as well as the ratio of ILC2 s in human peripheral blood(0.128% ± 0.013% vs 0.033% ± 0.003%,P <0.0001).Furthermore,the frequencies of ILC2 s in human peripheral blood significantly correlated with the miR-155 expression(Spearman's method.r = 0.4803,P = 0.013).2.The behavioral scores of the mice after the model establishment were 1.833 ± 0.307(control group),5.667 ± 0.333(AR group),7 ± 0.365(miR-155 agomir group),and 3.5 ± 0.224(miR-155 antagomir group).HE staining of nasal mucosa in AR mice showed obviously pathological changes in the nasal mucosa,including hyperemia,edema,necrosis,and aberrant structure.All of these pathological alterations were worsened after miR-155 agomir administration and ameliorated after administration of miR-155 antagomir.3.Compared with healthy controls,the expression of miR-155 in the nasal mucosa of AR mice was significantly increased(2.339 ± 0.206 vs 1.017 ± 0.052,P <0.0001),which was much higher after intranasal administration with miR-155 agomir(68.1 ± 12.9 vs 2.339 ± 0.206,P <0.0001).Nevertheless,miR-155 expression in the nasal mucosa of AR mice was significantly reduced after intranasal administration with miR-155 antagomir(1.429 ± 0.272 vs 2.339 ± 0.206,P <0.05).Upregulation of miR-155 markedly increased the levels of cytokines(IL-4,IL-5,IL-9 and IL-13).Moreover,in miR-155 antagomir mice,all these observations were reduced.Consistent with clinical specimen test results,ILC2 s were highly expressed in the nasal mucosa of AR mice compared with controls(3.347% ± 0.234% vs 1.767% ± 0.087%,P <0.0001).miR-155 agomir mice(6.053% ± 0.447% vs 3.347% ± 0.234%,P <0.001)showed much higher levels of ILC2 s compared to AR mice,whereas the lower levels of ILC2 s in miR-155 antagomir mice(2.403% ± 0.2249% vs 3.347% ± 0.234%,P <0.05).Conclusion:miR-155 and ILC2 are highly expressed in AR,and high expression of miR-155 can promote AR immune response by regulating ILC2 expression of Th2 cytokines,which is important for the prevention and control of AR. |
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