TAFA4 Potentiate Immunotherapy For Allergic Rhinitis By Induction Of Regulatory T Cells

Background:The prevalence of allergic rhinitis(AR)is on the rise and has become one of the major diseases affecting human health.Although allergen-specific immunotherapy(AIT)has been clinically effective,its long treatment time,poor patient compliance and side effects have led to unsatisfactory results.Failure of the regulatory cells in the immune system and their production of regulatory cytokines to control effector cells within a normal range,is an important factor in the pathogenesis of AR.TAFA4 is a neuropeptide with immunomodulatory effects.Therefore,the aim of this study is to clarify the immunomodulatory effects of TAFA4,to further induce the production of antigen-specific T cells in combination with AIT,to restore the immune tolerance function of the nasal mucosa,to suppress the abnormal immune response to AR,and to improve the efficacy of AIT.the efficacy of AIT.Methods:1.AR mouse model was established using ovalbumin(OVA)as the specific antigen,and the content of TAFA4 in the nasal irrigation fluid of experimental mice was analyzed by ELISA;AR mice were perfused with TAFA4 nasal drops,and the proportion of DC cells were detected by flow cytometry;the activity of various types of immune cells in the airways of AR mice was analyzed by RT-qPCR.2.The production of IL-10+CD11c+DC cells in the airway tissueswere analyzed by flow cytometry;RT-qPCR was used to detect IL-10;co-stimulatory factors on the surface of DC cells in the airway tissueswere analyzed by immunoblotting.The effect of TAFA4 on the genetic profile of DC cells was analyzed by RNAseq and bioinformatics.3.To detect the allergic inflammatory response in AR mice using TAFA4 combined with AIT treatment;to analyze the changes of Tr1 in vivo and its function after TAFA4/AIT treatment in experimental mice using flow cytometry.Results:1.TAFA4 was found to recruit and activate DC cells in airway tissues after nasal drip treatment of AR mice using TAFA4 protein.2.In vivo and in vitro experiments were conducted to elucidate the mechanism by which TAFA4 induces the secretion of IL-10 regulatory cytokines from DC cells activated by TAFA4 associated with the Fprl-MyD88-AKT signalling pathway and thus gains immune tolerance in AR mice.3.Based on the clarification of the role of TAFA4 in inducing the secretion of IL-10 cytokines by DC cells.TAFA4 combined with AIT treatment induced the production of antigen-specific Tr1 cells and enhanced the inhibitory effect of AIT on the allergic inflammatory response to AR in experimental animals was demonstrated.Conclusion:In this study,TAFA4 was found to activate DC cells to induce IL-10 expression in airway tissue associated with the Fprl-MyD88-AKT signaling pathway,and combined with AIT treatment in AR mice induced antigen-specific Trl cell production then enhanced the efficacy of AIT in inhibiting the allergic inflammatory of AR.