The Role And Mechanism Of IL-37 In Murine Allergic Rhinitis

Objective: An objective of this study was to assess the role of systemic application of Interleukin(IL)-37 in murine allergic rhinitis(AR).And further study to investigate the effect of IL-37 on the proliferation,differentiation and function of CD4+ Th cell subsets.Finally,this study seeks to explore the possible mechanism of IL-37 involved in AR.Methods: An ovalbumin(OVA)-induced AR murine model was established.Mice were randomly divided into three groups: the control group,the OVA group,and the IL-37 group.Ten min after the last challenge,the number of sneezes and nasal rubbings were recorded.Within24 h after the last challenge,all mice were decease.The concentrations of total IgE and Th cells effector cytokines(IFN-γ,IL-4,IL-5,IL-6,IL-10,and IL17a)in serum were determined by mouse ELISA kits.Mononuclear cells obtained from murine spleens to analyze Th1(CD4+IFN-γ+ T cells),Th2(CD4+IL-4+ T cells),Th17(CD4+IL-17a+ T cells),and Treg(CD4+CD25+Foxp3+ T cells)using flow cytometry.The nasal mucosa was removed and stained with hematoxylin and eosin(H&E),and the number of eosinophils was counted.Th cell-related transcription factors T-bet,GATA-3,Foxp3,RORγt,STAT3 and STAT6 were detected by Real-time PCR,and the protein expression of STAT3,STAT6,pSTAT3,and pSTAT6 was detected by Western blot.Results: An ovalbumin(OVA)-induced AR murine model was established.After IL-37 intervention,the number of sneezing and nasalrubbings,nasal mucosal infiltration with eosinophils,and serum total IgE production were found significantly attenuated in mice.Furthermore,the Th2 and Th17-related cytokines IL-4,IL-5,IL-6 and IL-17 a levels,CD4+IL-4+ and CD4+IL-17+ T cells proportions,GATA3 and RORγt mRNA levels,and STAT3/STAT6 protein phosphorylation levels were obviously lower than those of OVA control group(p < 0.05).However,there was no significant difference in the proliferation and differentiation of Th1 and Treg(CD4+IFN-γ+ and CD4 +CD25+Foxp3 T cells),the expression of the effector factors(IFN-γ and IL-10),and the key nuclear transcription factors(T-bet and Foxp3)among three groups.Conclusion: These results provide evidence of application of IL-37 attenuated the allergic process in an OVA-induced murine AR model.And this study has also shown that IL-37 suppressed the differentiation and function of Th2 and Th17 response via STAT6 and STAT3 signaling pathways.Thus IL-37 participates in the immune regulatory network of AR.