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Background: Human adipose tissue-derived stem cells (hADSCs) exert potent immunosuppressive effects in the allogeneic transplantation treatment. In mouse model of allergic rhinitis (AR), ADSCs partially ameliorated AR. However, no study has evaluated the potential therapeutic effects of hADSC-derived extracellular vesicles (hADSC-EVs) on AR., Methods: Female BALB/c mice were sensitized and challenged with ovalbumin (OVA) to induce AR. One day after the last nasal drop, each group received phosphate buffered saline (PBS) or hADSC-EVs treatment. Associated symptoms and biological changes were then assessed., Results: hADSC-EV treatment significantly alleviated nasal symptoms, and reduced inflammatory infiltration. Serum levels of OVA-specific IgE, interleukin (IL)-4 and interferon (IFN)-γ were all significantly reduced. The mRNA levels of IL-4 and IFN-γ in the spleen also changed accordingly. The T helper (Th)1/Th2 cell ratio increased. The treatment efficacy index of hADSC-EV was higher than that of all human-derived MSCs in published reports on MSC treatment of AR. ADSC-EVs exhibited a greater therapeutic index in most measures when compared to our previous treatment involving ADSCs., Conclusion: These results demonstrated that hADSC-EVs could ameliorate the symptoms of AR by modulating cytokine secretion and Th1/Th2 cell balance. hADSC-EVs could potentially be a viable therapeutic strategy for AR. Further animal studies are needed to elucidate the underlying mechanisms and to optimize potential clinical protocols., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yang, Pan, Zhang, Wang, lai, Zhou, Zhang, Fan, Deng, Gao and Yu.)

Background: Allergen-specific immunotherapy (AIT) is a causative treatment in allergic rhinitis (AR), comprising long-term allergen administration and over three years of treatment. This study is carried out for revealing the mechanisms and key genes of AIT in AR., Methods: The present study utilized online Gene Expression Omnibus (GEO) microarray expression profiling dataset GSE37157 and GSE29521 to analyze the hub genes changes related to AIT in AR. Based on limma package, differential expression analysis for the two groups (samples of allergic patients prior to AIT and samples of allergic patients undergoing AIT) was performed to obtain differentially expressed genes (DEGs). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEGs were conducted using DAVID database. A Protein-Protein Interaction network (PPI) was built and a significant network module was acquired by using Cytoscape software (Cytoscape, 3.7.2). Utilizing the miRWalk database, we identified potential gene biomarkers, constructed interaction networks of target genes and microRNAs (miRNAs) using Cytoscape software, and explore the cell type-specific expression patterns of these genes in peripheral blood using publicly available single-cell RNA sequencing data (GSE200107). Finally, we are using PCR to detect changes in the hub genes that are screened using the above method in peripheral blood before and after AIT treatment., Results: GSE37157 and GSE29521 included 28 and 13 samples, respectively. A total of 119 significantly co-upregulated DEGs and 33 co-downregulated DEGs were obtained from two datasets. The GO and KEGG analyses demonstrated that protein transport, positive regulation of apoptotic process, Natural killer cell mediated cytotoxicity, T cell receptor signaling pathway, TNF signaling pathway, B cell receptor signaling pathway and Apoptosis may be potential candidate therapeutic targets for AIT of AR. From the PPI network, 20 hub genes were obtained. Among them, the PPI sub-networks of CASP3, FOXO3, PIK3R1, PIK3R3, ATF4, and POLD3 screened out from our study have been identified as reliable predictors of AIT in AR, especially the PIK3R1., Conclusion: Our analysis has identified novel gene signatures, thereby contributing to a more comprehensive understanding of the molecular mechanisms underlying AIT in the treatment of AR., (© 2023. The Author(s).)

Objective: To explore the impact of PM 2.5 concentration in Shanghai on the incidence of allergic rhinitis（AR） in the population, and provide strategies for early warning and prevention of AR. Methods: Collect daily average concentrations of atmospheric pollutants monitored in Shanghai from January 1, 2017 to December 31, 2019, and clinical data of AR patients from five hospitals in Shanghai during the same period. We used a time-series analysis additive Poisson regression model to analyze the correlation between PM 2.5 levels and outpatient attendance for AR patients. Results: During the study period, a total of 56 500 AR patients were included, and the daily average concentration of PM 2.5 was（35.28±23.07）μg/m³. There is a correlation between the concentration of PM 2.5 and the number of outpatient attendance for AR cases. There is a positive correlation between the daily average number of outpatient for AR and levels of PM 2.5 air pollution（（ P <0.05）） . We found that every 10 μg/m³ increase in PM 2.5, the impact of on the number of AR visits was statistically significant on the same day, the first day behind, and the second day behind, with the strongest impact being the exposure on the same day. Every 10 μg/m³ increases in PM 2.5, the number of outpatient visits increased by 0.526% on the same day（95% CI 1.000 50-1.010 04）. Conclusion: The atmospheric PM 2.5 concentration in Shanghai is positively correlated with the number of outpatient for AR, and PM 2.5 exposure is an independent factor in the onset of AR. This provides an important theoretical basis for AR., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Objective: The concentration of exhaled NO and CO is considered as a candidate marker of respiratory inflammatory disease. This report discusses the exhaled NO and CO in the auxiliary diagnosis and evaluation of allergic rhinitis (AR)., Methods: 60 AR patients from October 2017 to March 2019, compared with 30 healthy controls. The severity of AR disease was distinguished by symptom score. Both groups were tested for exhaled nitric oxide through the nose or mouth and exhale carbon monoxide through the mouth. AR patients received glucocorticoid nasal spray for 1 month and were tested again for nNO, eNO, eCO, and symptom score., Results: Before treatment, all the nNO, eNO, and eCO of the AR group were higher than the control group. There were differences in the severe and moderate subgroup: severe > moderate > mild. eCO was not significantly different between the mild and control groups. The nNO, eNO, and eCO levels were positively correlated with symptom score. After treatment, nNO decreased significantly in the three subgroups; eNO and eCO in the severe AR group decreased significantly. Drawing the ROC curve, the area under curve (AUC) of nNO is 0.978. The AUC of eNO and eCO was 0.786 and 0.577, respectively., Conclusion: The nNO, eNO, and eCO in the AR group are higher than healthy people, which positively correlated with the severity of AR symptoms. The detection of nNO, eNO, and eCO can monitor the changes of AR. The detection of nNO level as an indicator of AR auxiliary diagnosis has high accuracy., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Chuanliang Zhao et al.)

Allergic rhinitis (AR) is a common otolaryngologic disease with frequent episodes of sneezing, clear nasal discharge flow and nasal congestion. The mechanisms of AR are complex and considered generally caused by the immune tolerance deficiency. Regulatory B cells (Bregs) are immunosuppressive cells that can modulate immune responses by the secretion of IL-10, IL-35, and tumor growth factor-β (TGF-β) and via the interaction of membrane surface molecules. However, Bregs are numerically deficient and/or dysfunctional in airway allergic diseases such as AR and allergic asthma, and the related mechanisms remain unclear. In this review, we summarize the role of Bregs in AR pathogenesis and highlight the importance of Bregs in maintaining immune tolerance. It is believed that further research on Bregs will contribute to developing new treatments and finding specific biomarkers that could help to predict disease progression., Competing Interests: The authors have no conflict of interest to declare.

Objective: In this study, the level of nasal nitric oxide（nNO）, exhaled nitric oxide（eNO）, and exhaled carbon monoxide（eCO） in patients with allergic rhinitis（AR） were tested, to explore the correlation between nNO, eNO, eCO and AR. Method: A total of 60 AR patientswere enrolled as the allergy group and then divided into mild, medium and severe subgroups according to symptom scores. 30 healthy volunteers were recruited as control group. The levels of nNO, eNO and eCO were detected in AR group, AR subgroups and control group. Result: The levels of nNO, eNO and eCO in AR group were higher than those in control group（ P <0.05）. nNO, eNO and eCO levels were positively correlated with symptom scores（ P <0.05）.Pairwise comparison was used between mild, moderate and severe subgroups. The difference of both nNO and eNO levels between mild, moderate and severe AR subgroups was statistically significant, severe>and moderate>were mild（ P <0.05）, but there was no significant difference in eNO levels between the mild AR subgroup and the control group（ P >0.05）. Level of eCO in severe AR subgroup was higher than those in moderate and mild AR subgroups（ P <0.05）, but there was no significant difference between mild, moderate AR subgroups and control group（ P >0.05）. nNO, eNO and eCO levels were used as indicators to evaluate the severity of AR, and the receiver operating characteristic（ROC） curves were plotted. The area under curve（AUC） was 0.978, 0.786 and 0.577, respectively. Taking eCO level as the indicator for disease assessment of severe AR, the AUC was 0.728. It showed that nNO had a high accuracy in evaluating the severity of AR, eNO had a certain accuracy in evaluating the severity of AR, and eCO had a certain accuracy in the assessment of severe AR. Conclusion: The detection of nNO, eNO and eCO levels can be used as an objective assessment method of the severity of AR., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Objective: To observe the effect of hydrogen-rich saline on the concentration of nitric oxide in the nose, and to explore the mechanism of its treatment of allergic rhinitis. Method: Twenty patients with moderate to severe persistent allergic rhinitis were enrolled in a randomized, double-blind, self-controlled study. The nasal cavity was lavaged with hydrogen-rich normal saline and normal saline, and the nasal nitric oxide（nNO） value was tested weekly. Result: The test value of nNO was correlated with the diagnosis and curative effect of allergic rhinitis. The difference of nNO test values before and after treatment of the two lavage fluids was statistically significant（ P <0.01）. Conclusion: Hydrogen-rich saline lavage can cause nNO change in nasal cavity which may be used in the treatment of allergic rhinitis., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Objectives: House dust mites, including Der p1, are common allergens. The current study was designed to explore the allergen-specific immune tolerance effects of Der p1-modified dendritic cells (DCs) through IL-4, IL-10 and IL-13 on an allergic rhinitis (AR) mouse model., Methods: A lentivirus was modified to express Derp1. Then, immature DCs from mice were infected with this modified lentivirus to generate a lenti-Derp1-GFP DCs. 24 mice were random divided into four groups (n = 6 each), AR mouse were sensitized by Derp1 allergens and treated with lenti-GFP DCs (GFP-DC/AR group), or lenti-Derp1-GFP DCs (Der p1-DC/AR group) and dexamethasone (Dex/AR group), mice in the control group were treated with PBS instead of Der p1 then also intraperitoneally injected with 5 × 10 6 lenti-GFP DCs/mouse. AR symptoms expressed by each mouse were recorded. The proportions of CD4 + CD25 + Foxp3 + regulatory T cells among CD4 + T cells in the peripheral blood, and mRNA and protein expression levels of IL-4, IL-10, and IL-13 were measured., Results: DCs infected with lenti-Derp1-GFP stimulated the maturation of DCs. Compared with the GFP-DC/AR group, mice in the Der p1-DC/AR group showed an ameliorated allergic response, a significant decrease in the levels of serum IgE, IgG1, and histamine, and a decrease in the expression of IL-4 and IL-13 mRNA and protein in the nasal mucosa. The expression of IL-10 increased in the Der p1-DC/AR group to a level similar to that observed in the Dex/AR group., Conclusions: These results indicate that Der p1-modified DCs have therapeutic potential for AR via downregulation of IL-4 and IL-13, and upregulation of IL-10., (Copyright © 2019 Elsevier B.V. All rights reserved.)

It is well known that CD4+CD25+Foxp3+Treg cells play an important role in the development of allergic rhinitis (AR); the defect of cell numbers and functions contribute to AR. Hydrogen has been proven effective in alleviating symptoms of AR. We herein aim to verify the protective effects of hydrogen on CD4+CD25+Foxp3+Treg cells in guinea pigs with AR and to explore the effect of hydrogen-rich saline (HRS) on CD4+CD25+Foxp3+Treg cells in animals with AR and investigate the underlying anti-inflammatory mechanism. Eighteen guinea pigs were randomly divided into three groups (control group/AR group/AR-HRS group). The guinea pigs were injected with hydrogen-rich saline (AR-HRS group) for 10 days after sensitization. The control group was injected with an equal volume of normal saline. The number of sneezes, degree of runny nose, and nasal-rubbing movements were scored. Peripheral blood eosinophil count was recorded. The proportions of Th1/Th2 of the peripheral blood and the CD4+CD25+Foxp3+T cells in the CD4+T cells of the spleen and peripheral blood were determined by flow cytometry. The content of interleukin (IL)-10 and transforming growth factor (TGF)-β in the serum was detected by enzyme-linked immunosorbent assay (ELISA). The protein and mRNA expression of Foxp3, IL-10, and TGF-β were determined by Western blot, immunofluorescence, and real-time PCR analysis, respectively. Scores of symptoms, number of eosinophils,and nasal mucosa damage were dramatically reduced after HRS treatment. HRS increased the expression of Foxp3, IL-10, TGF-β, and number of CD4+CD25+Foxp3+Treg cells, which were reduced in AR. HRS also revised the dysregulation of Th1/Th2 balance. Both the number and biological activity of CD4+CD25+Foxp3+Treg cells increased with up-regulation of Th1/Th2 after HRS administration. HRS could play a protective role in attenuating AR through improving the proportion and functions of CD4+CD25+Foxp3+Treg cells.

The CD4 + CD25 + Foxp3 + regulatory T cells (Tregs) are known to regulate Th2-induced allergic rhinitis (AR). In this study, we evaluated the efficacy of Derp1-modified dendritic cells (DCs) in AR immunotherapy. Derp1 was synthesized and transfected into DCs to generate Derp1-modified DCs. Phenotypes of Derp1-modified DCs were analyzed with flow cytometry using antibodies against DC markers CD11c, CD11b, CD59, CD103 and Toll-like receptor 1(TLR1). Four groups of subject mice were formed; the controls were treated with immature DCs, while the AR mice models were sensitized with Derp1(AR) and treated with DCs(DC-AR) or Derp1-modified DCs (Derp1DC-AR). The frequency of sneezing and scratching, eosinophil cell count, and Th1/Th2 ratio in the spleen were measured for all groups. The percentage of CD4 + CD25 + Foxp3 + Tregs in peripheral blood mononuclear cells was measured using flow cytometry; serum IgE, IgG1, and histamine were measured using enzyme-linked immunosorbent assay; expression levels of transcription factors T-bet, GATA3, Foxp3+ and IL-10 were analyzed using reverse transcription-polymerase chain reaction, and Western blot used in analyzed expression of Foxp3+ and IL-10 in nasal mucosa. Treatment with Derp1-modified DCs ameliorated the allergic response. The Derp1DC-AR group had significantly lower eosinophil cell count and the IgE, IgG1, and histamine levels than the AR and DC-AR groups, and higher mRNA levels of Th1 transcription factors T-bet, IL-10 and Foxp3 in nasal mucosa than DC-AR mice, but Th2 transcription factors GATA3 mRNA expression level has the opposite results. Furthermore, the Th1/Th2 ratio and percentage of CD4 + CD25 + Foxp3 + Tregs was significantly lower in the AR group (p<0.05), but higher in the Derp1DC-AR group than in the control group (p<0.01). Thus, the Derp1-modified DCs increased the percentage of CD4 + CD25 + Foxp3 + Tregs and influenced the balance of Th1/Th2, showing an immunotherapeutic effect against AR., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: The discovery of carbon monoxide (CO) and hydrogen sulfide (H2S) as pathogenic signaling molecules in airway-related diseases has led to significant insights into the pathophysiologic mechanisms underlying the development of allergic rhinitis (AR). The potential crosstalk between CO and H2S signaling pathways in AR has not been adequately investigated. This study was performed to elucidate the mechanistic relationship between CO and H2S in AR., Study Design: Experimental prospective animal study., Setting: Animal laboratory of Tongji Hospital, Tongji University, Shanghai, China., Subjects and Methods: A well-established model of AR was used whereby guinea pigs (N=24) were randomly divided into 4 treatment groups (n=6 for each group): The first group received ovalbumin only; the second group was administered exogenous hemin, a CO-binding metalloporphyrin; the third group received zinc protoporphyrin, an inhibitor of heme oxygenase-1. A control group was challenged using only saline. Symptoms of AR were recorded, and quantitation of plasma CO and H2S levels was performed. Expression of heme oxygenase-1 and H2S-generating enzyme cystathionine-γ-lyase (CSE) were measured from nasal mucosa., Results: Plasma CO and heme oxygenase-1 expression levels of nasal mucosa were significantly increased in the AR group compared to controls, whereas H2S concentrations were significantly decreased. Exogenous administration of CO exacerbated allergic symptoms, resulting in higher levels of both CO and heme oxygenase-1 expression, and a further reduction in H2S levels and CSE expression. Zinc protoporphyrin decreased CO concentrations and increased levels of both H2S and CSE expression., Conclusions: Results indicated an inverse relationship between H2S levels and CO in the pathogenesis of AR., (© American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.)

Dendritic cells (DCs) is known as the most potential and professional antigen presenting cells (APC), it mainly involves in the cellular immunity and T cell dependent humoral immunity, which plays a key role in the immune response and is one of the most hot areas in immunology in recent years. DCs plays a key role in allergic rhinitis (AR) and is one of the most important mechanism of AR treating by sublingual immunotherapy (SLIT). This article reviewed the mechanism of the role of DCs in AR and AR treating by SLIT.