OBJECTIVE: To investigate the changes in percentage of GATA3⁺ regulatory T (Treg) cells in patients with allergic rhinitis (AR) and mouse models. METHODS: The nasal mucosa specimens were obtained from 6 AR patients and 6 control patients for detection of nasal mucosal inflammation. Peripheral blood mononuclear cells (PBMC) were collected from 12 AP patients and 12 control patients to determine the percentages of Treg cells and GATA3⁺ Treg cells. In a C57BL/6 mouse model of AR, the AR symptom score, peripheral blood OVA-sIgE level, and nasal mucosal inflammation were assessed, and the spleen of mice was collected for detecting the percentages of Treg cells and GATA3⁺ Treg cells and the expressions of Th2 cytokines. RESULTS: Compared with the control patients, AR patients showed significantly increased eosinophil infiltration and goblet cell proliferation in the nasal mucosa (P < 0.01) and decreased percentages of Treg cells and GATA3⁺ Treg cells (P < 0.05). The mouse models of AR also had more obvious allergic symptoms, significantly increased OVA-sIgE level in peripheral blood, eosinophil infiltration and goblet cell hyperplasia (P < 0.01), markedly lowered percentages of Treg cells and GATA3⁺ Treg cells in the spleen (P < 0.01), and increased expressions of IL-4, IL-6 and IL-10 (P < 0.05). CONCLUSION The percentage of GATA3⁺ Treg cells is decreased in AR patients and mouse models. GATA3⁺ Treg cells possibly participate in Th2 cell immune response, both of which are involved in the occurrence and progression of AR, suggesting the potential of GATA3⁺ Treg cells as a new therapeutic target for AR.
Animals ; Mice ; Cytokines/metabolism* ; Disease Models, Animal ; GATA3 Transcription Factor ; Inflammation ; Leukocytes, Mononuclear/metabolism* ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Nasal Mucosa/metabolism* ; Ovalbumin ; Rhinitis, Allergic/therapy* ; T-Lymphocytes, Regulatory ; Th2 Cells/metabolism* ; Humans

Objective To investigate the role of microRNA-18a (miR-18a) in the pathogenesis of allergic rhinitis in mice. Methods Twenty-two BALB/c mice were randomly divided into a blank group, a model group and a miR-18a group. Mice in the model group and the miR-18a group were injected intraperitoneally with obumin (OVA) suspension to prepare allergic rhinitis models, and mice in the miR-18a group were simultaneously given lentiviral vector plasmid for overexpression of miR-18a. Allergy symptoms were evaluated by the behavioral score and HE staining. The plasma levels of interleukin-1β (IL-1β), IL-6 and tumor necrosis factor α (TNF-α) were measured by ELISA. The distribution of CD45⁺ cells in nasal mucosa was measured by immunofluorescence histochemistry, and CD45⁺ cells in nasal lavage fluid were measured by flow cytometry. The mRNA expression levels of IL-1β, IL-6 and TNF-α in nasal mucosa tissues were measured by fluorescence quantitative PCR, and the protein expressions of Toll like receptor 4 (TLR4), nuclear factor κB p65 (NF-κB p65), inhibitor of NF-κB α (IκBα) and phosphorylated IκBα (p-IκBα) in nasal mucosa were measured by Western blot analysis. Results Compared with the blank group, the plasma levels of IL-1β, IL-6, and TNF-α in the model group increased significantly. The number of CD45⁺ cells in both nasal mucosa tissue and nasal irrigation fluid increased, and the mRNA levels of IL-1β, IL-6 and TNF-α and the protein expression levels of TLR4, NF-κB p65 and p-IκBα in nasal mucosa increased. Compared with the model group, the plasma levels of IL-1β, IL-6 and TNF-α in the miR-18a group decreased significantly. The number of CD45⁺ cells in both nasal mucosa tissue and nasal lavage fluid decreased, and the mRNA levels of IL-1β, IL-6 and TNF-α and the exprotein expression levels of TLR4, NF-κB p65 and p-IκBα in nasal mucosa decreased. Conclusion miR-18a can inhibit the occurrence and development of allergic rhinitis, and its molecular mechanism is related to the inhibition of TLR4/NF-κB pathway activation.
Animals ; Mice ; Disease Models, Animal ; Inflammation ; Interleukin-6/genetics* ; MicroRNAs/genetics* ; NF-kappa B/metabolism* ; NF-KappaB Inhibitor alpha ; Rhinitis, Allergic ; RNA, Messenger ; Toll-Like Receptor 4/metabolism* ; Tumor Necrosis Factor-alpha/genetics*

Objective To investigate the expressions of IL-18, IL-18 binding protein isoform a (IL-18BPa) and IL-18 receptor α (IL-18Rα) in blood CD4⁺ Th2 cells of patients with allergic rhinitis (AR) and the effects of allergens on their expressions. Methods Blood samples of AR patients and healthy control subjects (HCs) were collected. Peripheral blood mononuclear cells (PBMCs) and CD4⁺ T cells sorted by immunomagnetic beads were stimulated by crude extract of Artemisia sieversiana wild allergen (ASWE), Platanus pollen (PPE) and house dust mite extract (HDME). Flow cytometry was used to detect the expression of IL-18, IL-18BPa and IL-18Rα in CD4⁺ Th2 cells, and BioPlex was used to detect the level of plasma IL-4 and analyze its correlation with the proportion of IL-18⁺ Th2 cells. Results Compared with HCs, the proportion of IL-18⁺ cells was increased in Th2 cells of AR patients; MFI of IL-18 was increased, while that of IL-18Rα was decreased. Moreover, allergens induced IL-18 and IL-18Rα expression in sorted CD4⁺ Th2 cells of HCs and induced IL-18Rα in that of AR patients. Additionally, elevated plasma IL-4 level was found in AR patients, which was moderately correlated with the percentage of IL-18⁺ Th2 cells. Conclusion Allergens may be involved in the pathogenesis of AR by inducing expression of IL-18 in peripheral blood CD4⁺ Th2 cells.
Humans ; Th2 Cells ; Interleukin-18/metabolism* ; Up-Regulation ; Leukocytes, Mononuclear/metabolism* ; Interleukin-4/metabolism* ; Rhinitis, Allergic/metabolism* ; Allergens ; Cytokines/metabolism*

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected 660 million people and resulted in 6.7 million deaths. At present, a variety of risk factors related to the severity of COVID-19 have been identified, but whether allergic rhinitis and asthma will affect SARS-CoV-2 infection remains controversial. In general, there is no sufficient evidence to support that allergic rhinitis or asthma is a risk factor for increasing the rate of SARS-CoV-2 infection or aggravating the disease. Some studies even show that atopy may be a protective factor to alleviate SARS-CoV-2 infection, which is related to the decreased expression of angiotensin-converting enzyme 2, the receptor required for SARS-CoV-2 to enter cells, in atopic individuals. This paper reviews the influence of the severity and treatment of allergic rhinitis and asthma on SARS-CoV-2 infection, in order to provide some references for establishing strategies for prevention, risk stratification and treatment of COVID-19.
Humans ; COVID-19 ; SARS-CoV-2/metabolism* ; Peptidyl-Dipeptidase A/metabolism* ; Asthma/therapy* ; Rhinitis, Allergic

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected 660 million people and resulted in 6.7 million deaths. At present, a variety of risk factors related to the severity of COVID-19 have been identified, but whether allergic rhinitis and asthma will affect SARS-CoV-2 infection remains controversial. In general, there is no sufficient evidence to support that allergic rhinitis or asthma is a risk factor for increasing the rate of SARS-CoV-2 infection or aggravating the disease. Some studies even show that atopy may be a protective factor to alleviate SARS-CoV-2 infection, which is related to the decreased expression of angiotensin-converting enzyme 2, the receptor required for SARS-CoV-2 to enter cells, in atopic individuals. This paper reviews the influence of the severity and treatment of allergic rhinitis and asthma on SARS-CoV-2 infection, in order to provide some references for establishing strategies for prevention, risk stratification and treatment of COVID-19.
Humans ; COVID-19 ; SARS-CoV-2/metabolism* ; Peptidyl-Dipeptidase A/metabolism* ; Asthma/therapy* ; Rhinitis, Allergic

OBJECTIVE: To investigate the differential characteristics of plasma mircoRNA (miRNA) expression profile in the patients of moderate-to-severe allergic rhinitis treated with acupuncture so as to provide an index for screening the potential biomarkers of acupuncture efficacy. METHODS: Of 33 patients of moderate-to-severe allergic rhinitis underwent acupuncture, the superior efficacy patients (superior efficacy group, 3 cases) and the inferior efficacy patients (inferior efficacy group, 3 cases) were selected. Using human miRNA microarray technology, the differences in plasma miRNA expression before and after treatment were analyzed in the patients of two groups. Besides, 10 cases of superior efficacy and 10 cases of inferior one were selected respectively among the patients of moderate-to-severe allergic rhinitis treated with same acupuncture regimen; and the real-time PCR was used to validate miRNAs of differential expression determined by microarray technology. The bioinformatics analysis was performed for miRNAs of significant differences in expression so as to predict the potential functional target genes, and then, the predicted target genes were annotated in reference with the databases of gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG). RESULTS: Before treatment, there were 51 miRNAs of differential expression between two groups, of which, the expression levels of 26 miRNAs were up-regulated and those of 25 miRNAs were down-regulated. Compared with before treatment, 33 miRNAs presented differential expression in the superior efficacy group after treatment. The results of real-time PCR showed that the expression levels of hsa-miR-126-3p, hsa-miR-15a-5p, hsa-miR-494-3p and hsa-miR-574-5p were consistent with the results of microarray analysis in tendency. GO/KEGG analysis indicated that miRNAs with significant differences of expression between two groups were involved in regulating various biological processes, molecular functions and signaling pathways. CONCLUSION Plasma miRNA-mediated biological processes may be associated with the efficacy response of acupuncture in treatment of moderate-to-severe allergic rhinitis. Plasma miRNAs of differential expression may be the potential non-invasive biomarkers to predict the effectiveness of acupuncture on moderate-to-severe allergic rhinitis.
Acupuncture Therapy ; Humans ; MicroRNAs/metabolism* ; Rhinitis, Allergic/therapy* ; Signal Transduction

Antibiotic exposure-induced dysbiosis of the intestinal flora increases the risk of developing allergic rhinitis. Hence, regulating the balance of intestinal flora may be useful for preventing and treating allergic rhinitis. However, the underlying mechanism is unclear. Dendrobium nobile (Shihu) exhibits anti-inflammatory and immune activities. Hence, in this study, we investigated the mechanism via which Shihu may improve allergic rhinitis. Mouse models of allergic rhinitis with intestinal flora dysbiosis (Model-D, antibiotics induce intestinal flora dysbiosis with ovalbumin-induced allergy) and normal intestinal flora with allergic rhinitis (Model-N, ovalbumin-induced allergy) were established. The effect of Shihu on intestinal flora and inflammation caused during allergic rhinitis were analyzed. Allergic symptoms, infiltration of hematoxylin and eosin in the lungs and nose, and the release of various factors [interleukin (IL)-2, IL-4, IFN-γ, IL-6, IL-10, and IL-17] in the lungs were evaluated. The results indicate that intestinal flora dysbiosis exacerbated lung and nose inflammation in allergic rhinitis. However, treatment with the Shihu extract effectively reversed these symptoms. Besides, the Shihu extract inhibited the PI3K/AKT/mTOR pathway and increased the level of Forkhead box protein in the lungs. Additionally, the Shihu extract reversed intestinal flora dysbiosis at the phylum and genus levels and improved regulator T cell differentiation. Furthermore, in the Model-D group, the Shihu extract inhibited the decrease in the diversity and abundance of the intestinal flora. Screening was performed to determine which intestinal flora was positively correlated with Treg differentiation using Spearman's correlation analysis. In conclusion, we showed that Shihu extract restored the balance in intestinal flora and ameliorated inflammation in the lungs of allergic rhinitis mice and predicted a therapeutic new approach using Traditional Chinese Medicine to improve allergic rhinitis.
Animals ; Cytokines/metabolism* ; Dendrobium ; Disease Models, Animal ; Drugs, Chinese Herbal/pharmacology* ; Dysbiosis/drug therapy* ; Gastrointestinal Microbiome ; Inflammation/drug therapy* ; Mice ; Mice, Inbred BALB C ; Ovalbumin ; Phosphatidylinositol 3-Kinases ; Pneumonia ; Rhinitis, Allergic/metabolism*

Objective: To clarify the chemotactic characteristics of type 2 helper T cells (Th2 cells) and type 2 follicular helper T cells (Tfh2 cells) in peripheral blood of patients with allergic rhinitis (AR), and to explore the associations between the chemokine receptors expression and the levels of antigen-specific IgE (sIgE) and the severity of the disease. Methods: The peripheral blood mononuclear cells of 41 patients with AR (20 males and 21 females, aged 35.0 (24.5, 47.0) years) and 42 healthy controls (24 males and 18 females, aged 35.0 (24.8, 46.5) years) treated in Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from April 2017 to February 2018 were isolated. The expressions of chemokine receptor (CCR)2, CCR3, CCR4, CCR5, CCR7, CCR8, chemokine C-X3-C-motif receptor 1 (CX3CR1) and C-X-C motif receptor 4 (CXCR4) in Th2 and Tfh2 cells were explored by fluorescence activated cell sorting (FACs). The relationship between the expression of these chemokine receptors in Th2 cells and Tfh2 cells and the levels of serum sIgE and the scores of visual analogue scale (VAS) was analyzed. Graphpad prism 7.0 software was used for statistical analysis. Results: The significant differences in chemotactic characteristics between Th2 cells and Tfh2 cells in the control group were found: Th2 cells highly expressed chemokine receptors CCR2, CCR3, CCR5, CCR8 and CX3CR1, while Tfh2 cells highly expressed immune cell homing chemokine receptors CCR7 and CXCR4. AR patients, compared to the control, expressed higher levels of CCR2, CCR5 and CX3CR1 on peripheral Th2 cells(all P<0.01). At the same time, the proportion of CCR2⁺and CCR5⁺Th2 cells was positively correlated with VAS score (r value was 0.58 and 0.61, respectively, both P<0.01). In AR patients, higher expression levels of CCR7 on Tfh2 cells were detected (P<0.01), and the proportion of CCR7⁺Tfh2 cells was positively correlated with the level of serum sIgE (r=0.51, P<0.01). Conclusion: The percentage of CCR2⁺ and CCR5⁺ Th2 cells in peripheral of AR patients can reflect the severity of AR to some extent, while the percentage of CCR7⁺ Tfh2 cells is positively correlated with the level of serum sIgE.
Adult ; Female ; Humans ; Leukocytes, Mononuclear ; Male ; Middle Aged ; Rhinitis, Allergic/metabolism* ; Severity of Illness Index ; Th2 Cells

Objective: Transcriptome sequencing and bioinformatics analysis were performed on the gene expression of nasal epithelial cells in patients with seasonal allergic rhinitis (AR) and perennial AR, so as to obtain the differences in the gene expression of nasal epithelial cells between seasonal AR and perennial AR. Methods: The human nasal epithelial cell line(HNEpC) was cultured in vitro, treated with 100 μg/ml mugwort or house dust mite (HDM) extracts for 24 hours. Total cell RNA was extracted, and quantitative real-time polymerase chain reaction (qPCR) was used to detect the expression of cytokines, including IL-6, IL-8, IL-33 and thymic stromal lymphopoietin (TSLP). From November 2019 to November 2020, 3 seasonal AR patients, 3 perennial AR patients, and 3 healthy controls who attended the Department of Otolaryngology Head and Neck Surgery, China-Japan Union Hospital of Jilin University were analyzed. The patients' primary nasal epithelial cells were cultured in vitro, treated with corresponding allergens for 24 hours. Total RNA was extracted for transcriptome sequencing, and the sequencing results were analyzed by bioinformatics. Results: The qPCR results showed that the cytokines IL-6, IL-8, IL-33 and TSLP of HNEpC treated with mugworts extracts and HDM extracts had the same trend of change. After the nasal epithelial cells from patients with seasonal AR and perennial AR were treated with corresponding allergens, there were differences in biological processes and signal pathways between those and control. Gene ontology (GO) enrichment analysis showed that the differentially expressed genes (DEG) in AR patients allergic to mugwort were mainly enriched in the oxidation-reduction process, the negative regulation of apoptosis process, and the cell adhesion; the DEG in AR patients allergic to HDM were mainly enriched in cell adhesion, the negative regulation of cell proliferation and the response to drug. Enrichment analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway showed that the DEG of AR patients allergic to mugwort were significantly enriched in arachidonic acid metabolism, p53 signaling pathway and transforming growth factor β (TGF-β) signaling pathway, while the DEG of AR patients allergic to HDM were mainly enriched in cells cycle, Fanconi anemia pathway and DNA replication. Gene Set Enrichment Analysis (GSEA) showed that the inflammatory response, TNF-α/NF-κB signaling pathway and IL-2/STAT5 signaling pathway were significantly up-regulated in AR patients allergic to mugwort, indicating the promotion of inflammatory response; and AR patients allergic to HDM had significant down-regulation of G2M, E2F, and MYC, indicating the inhibition of cell proliferation. The protein-protein interaction network showed that TNF and CDK1 were the most interacting proteins in mugwort and HDM allergic AR patients, respectively. Conclusion: Seasonal AR and perennial AR may affect the different biological processes and signal pathways of nasal epithelial cells, leading to differences in the occurrence and development of AR.
Allergens ; Animals ; Computational Biology ; Cytokines/metabolism* ; Epithelial Cells/metabolism* ; Gene Expression ; Humans ; Interleukin-33/metabolism* ; Interleukin-6/metabolism* ; Interleukin-8 ; Nasal Mucosa/metabolism* ; Plant Extracts/metabolism* ; Pyroglyphidae ; RNA/metabolism* ; Rhinitis, Allergic/metabolism* ; Rhinitis, Allergic, Perennial ; Rhinitis, Allergic, Seasonal ; Seasons

Objective: To explore the relationship between NLRP3-mediated pyroptosis and olfactory dysfunction (OD) in allergic rhinitis (AR), and to evaluate the therapeutic potential of CY-09, a selective NLRP3 inhibitor for OD. Methods: An AR mouse model was established with ovalbumin, and the olfactory function of AR mice was detected by the buried food pellet test. Mice with OD were intraperitoneally injected with CY-09 or saline. The activation of microglia and astrocytes in olfactory bulb was detected by immunohistochemistry. The expression level of pyroptosis associated protein was detected by Western blot. The level of pyroptosis associated proinflammatory factor mRNA was determined by real-time PCR. SPSS 24.0 software was used for statistical analysis. Results: After the test, ovalbumin successfully established AR mice model, in which 52.5% (21/40) of them showed OD. The number of activated microglia and astroglia in olfactory bulb tissue in OD group were more than those in non-OD group (all P<0.05). Compared with the control group, the expression of NLRP3, caspase-1 and gasdermin D (GSDMD) was significantly increased in the olfactory bulb of the OD group (all P<0.05). CY-09 could significantly reduce the level of NLRP3, caspase-1, GSDMD, IL-1β and IL-18 expression, and inhibite the activation of microglia and astrocytes in the olfactory bulb tissues (all P<0.05). Conclusion: NLRP3-mediated pyroptosis is closely related to the OD associated with AR. CY-09 could improve the olfactory function in AR mice, which may be related to blocking the NLRP3-mediated pyroptosis.
Animals ; Caspases/therapeutic use* ; Disease Models, Animal ; Humans ; Inflammasomes/therapeutic use* ; Mice ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Ovalbumin ; Pyroptosis ; Rhinitis, Allergic/drug therapy* ; Smell