Abstract

BackgroundStudies have shown that the number and function of type II innate lymphoid cells (ILC2) in peripheral blood of allergic rhinitis (AR) children increased significantly. This study aims to evaluate the role of miR-375 in the regulation of the differentiation and function of ILC2 through both in vivo and in vitro studies. MethodsThe expression of miR-375, thymic stromal lymphopoietin (TSLP) and the frequency of ILC2 were detected and compared between AR children and controls by real-time polymerase chain reaction (PCR), enzyme-linked immunosorbnent assay (ELISA) and flow cytometry, respectively. The miR-375 mimics or inhibitors were transfected into human nasal epithelial cells (HNECs), and the production of TSLP was detected by ELISA. HNECs and ILC2s were co-cultured to explore the role of miR-375 on ILC2s. AR mice models were established to prove the effect of miR-375 on ILC2s in vivo. ResultsThe expression of TSLP, miR-375, and the frequency of ILC2 were significantly higher in AR compared with controls. We found that the TSLP expression by HNECs were significantly higher when transfected with miR-375 mimics than in those transfected with miR-control and miR-375 inhibitor. In the coculture system, HNECs transfected with miR-375 mimics promote the type II cytokines production by ILC2, and this effect was blocked by anti-TSLP. Our results also showed that the miR-375 inhibitors attenuate allergic symptoms and production of type II cytokines in AR mice. ConclusionsOur findings suggest that miR-375-mediated regulation of ILC2 cells through TSLP, providing new potential treatment target for AR.

Highlights

  • Allergic rhinitis (AR) is one of the most common chronic diseases in otorhinolaryngology

  • We found that the thymic stromal lymphopoietin (TSLP) expression by human nasal epithelial cells (HNECs) were significantly higher when transfected with miR-375 mimics than in those transfected with miR-control and miR375 inhibitor

  • HNECs transfected with miR-375 mimics promote the type II cytokines production by Type II innate lymphoid cells (ILC2), and this effect was blocked by anti-TSLP

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Summary

Introduction

Allergic rhinitis (AR) is one of the most common chronic diseases in otorhinolaryngology. Clinical symptoms such as nasal obstruction, itching, sneezing, and runny nose caused by AR have a serious impact on the quality of life of children and consume huge social and medical resources.[1]. MiRNA is an evolutionarily conserved small noncoding RNA, consisting of about 22 nucleotides.[5] MiR-375 belongs to the highly conservative miRNA family and was first found to have the function of regulating insulin secretion in pancreatic tissue.[6] In recent years, studies showed that miR-375 plays important roles in Th2-related diseases and TSLP production.[7,8,9] its role in ILC2 cells was not clear. This study aims to evaluate the role of miR-375 in the regulation of the differentiation and function of ILC2 through both in vivo and in vitro studies

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