Tfhs Exosomes Derived From Allergic Rhinitis Mice Promote DCs Maturation Through MiR-142-5p/CDK5/STAT3 Pathway

BackgroundDendritic cells(DCs)play an important role in allergen signal presentation.Many studies showed that follicular helper T cells(Tfhs)are related to allergic rhinitis(AR).However,the relationship between Tfhs and DCs and the mechanism of their effects on AR remain unclear.ObjectiveTo explore the mechanism of Tfhs on DCs maturation in AR.MethodsTfhs were isolated from OVA-sensitized mice and co-cultured with DCs derived from mouse bone.DCs maturity was monitored using flow cytometry and immunofluorescence staining.Exosomes of Tfhs were extracted and analyzed using miRNA sequencing to isolate differentially expressed gene.The TargetScan website predicts that CDK5 is a direct target gene,which is verified in a dual luciferase assay.DCs were treated with miR-142-5p mimics or inhibitors or transfected with CDK5 small interfering RNA to verify the regulatory effects of miR-142-5p and CDK5 on DCs maturation.How CDK5 regulates STAT3 signaling pathway was investigated to elucidate the molecular mechanism of DCs maturation.In vivo,the exosomes of AR-derived Tfhs was injected intravenously to detect their promotion of AR.ResultsTfhs and their exosomes derived from AR contributed to DCs maturation.MiRNA-seq result showed that miR-142-5p which its sequence is similar with miR-142b was the differentially decreased gene.TargetScan website predicted that CDK5 was the target gene for direct action of miR-142-5p.By detecting the changes of the expression levels of miR-142-5p and CDK5 for the DCs maturation,it was demonstrated that miR-142-5p inhibits DCs maturation by inhibiting CDK5 expression.CDK5-regulated STAT3 signaling pathway activity during the DCs maturation,and inhibition of the STAT3 signaling pathway can reverse the regulation of miR-142-5p/CDK5 on DCs maturation.Finally,in vivo experiments indicated that the injection of AR-derived Tfhs promoted AR by Th2 response in mice.ConclusionTfhs-derived exosomes induce DCs maturation by regulating miR-142-5p/CDK5/STAT3 signaling pathway,and promote the occurrence of AR by Th2 response.