| Objective:Allergic rhinitis(AR)is a common allergic disease.Currently,a variety of studies have demonstrated that semaphorins which were originally discovered in nerve system with guidance activity play important regulatory roles in immune system.It was reported that semaphorin 3A(sema3A),one member of semaphorins family,could alleviate nasal rubbing and sneezing symptoms in allergic rhinitis(AR)mice by inhibiting the innervation of nerve fibers.However,whether sema3A has immunomodulatory roles in AR was unknown.This study was investigated to explore the effects and mechanisms of sema3A on AR.Firstly,the sema3A expression in serum and nasal mucosa of AR patients and mice model were examined to clarify the role of sema3A in AR.Then,a sema3A administrated AR mice model was made to examine the immunoregulatory effect of sema3A on AR mice.Lastly,the expression of peptides,such as NKA,NPK,VIP and nociceptin,as well as cytokines including IL-4 and IFN-? in the nasal mucosa were detected to explore the regulatory of sema3 A in AR by neuroendocrine-immune interaction.Methods:1.Sema3A expression in the serum and nasal mucosa of AR patients and mice model was detected by ELISA and immunofluorescence.The expression of OVA specific IgE,IL-4 and IFN-? were examined by ELISA.The percentages of Th1,Th2,Th17,Treg and Breg in the spleen were examined by flow cytometry.HE and PAS staining were conducted to investigated the histologic changes of AR mice model.2.A total of 32 female BALB/c mice were randomly divided into four groups:negative control group,AR group,AR+Sema3A group and AR+Saline group.Nasal symptoms,OVA-specific IgE production and cytokines(including IL-4,IFN-?,IL-10 and IL-17)concentration were compared among the four groups.The frequencies of CD4+IL-17+Th17 cells,CD4+CD25+Foxp3+Treg cells and CD 19+IL-10+Breg cells in spleen were analyzed by flow cytometry.3.The expression of neuropeptides,including NKA,NPY,VIP and nociceptin,as well as IL-4 and IFN-? in the nasal mucosa were detected by immunofluorescence.A correlation analysis of NKA,VIP,IL-4 and IFN-? was also made to explore the relation between neuropeptide and cytokines.Results:1.The expression of sema3A in serum and nasal mucosa of AR patients and mice model were significantly lower compared to the controls.The concentrations of OVA specific IgE and IL-4 in AR group were significantly higher than the controls,while the concentrations of IFN-y were lower compared to the controls.Compared to the controls,the percentages of Th1,Treg and Breg cells were significantly decreased,while the percentages of Th2 and Th17 cells were increased in the AR group.Moreover,increased EOS infiltration and PAS-postive cells were observed in AR mice when compared to the controls.2.The nasal rubbing frequencies in AR+Sema3A group was lower than that in the AR group.The levels of OVA-specific IgE,IL-4,IL-17A as well as the percentages of CD4+IL-17+Th17 cells were lower in AR+Sema3A group than that in the AR group and AR+Saline group.The levels of IFN-y and IL-10 as well as the percentages of CD4+CD25+Foxp3+Treg cells were higher in AR+Sema3A group than that in the AR group.3.A increased expression of NKA,VIP and NPY were observed in AR mice compared to the controls.The expression of NKA,VIP and IL-4 were significantly lower in sema3A mice while the expression of IFN-y was increased compared to the AR mice.Moreover,a positive correlation between NKA,VIP and IL-4 while,a negative correlation of VIP and IFN-? were observed.Conclusion:1.Sema3A was lower expressed in AR.2.Our results demonstrated that sema3A could suppress allergic inflammation in AR via modulating Th1/Th2 imbalance and Th17/Treg imbalance.3.Breg cells may associated with AR and sema3A could suppress allergic inflammation by increasing the expression of Breg cells.4.Sema3A could have an important role in the pathogenesis of AR by regulating neuroendocrine-immune interaction. |
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