ABSTRACT
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.
Subject(s)
Animals , Mice , Humans , 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/metabolismABSTRACT
Objective@#To study the expression and significance of Notch1-Jagged1 in nasal mucosa of allergic rhinitis (AR) mouse model in various stages and in the serum of AR patients.@*Methods@#Thirty-six mice were divided into 3 groups: control group, basal sensitization group (OVA) and OVA/AR group, with 12 mice in each group. Allergic symptom in each group were scored after AR model establishment. HE staining method was used to observe the nasal mucosa eosinophils infiltration. ELISA was used to detect the serum level of total IgE. Flow cytometry was used to detect the change of Treg cells in each group. Western blot was used to detect the expression of Notch1 and Jagged1 in nasal mucosa. Flow cytometric bead array (CBA) was used to detect the level of Th1/Th2/Th17 cytokines in splenic lymphocytes. The serum was obtained from 50 patients with AR and 30 control volunteers in Department of Otorhinolaryngology Head and Neck Surgery, Renmin Hospital of Wuhan University from June to October 2017. ELISA was used to detect the expression of Notch1 and Jagged1.@*Results@#Compared with the control group, the allergy symptom, the number of nasal mucosal eosinophils and the level of total IgE were not significantly different in basal sensitization group, but increased significantly in OVA/AR group (6.11±0.78 vs 0.67±0.50, 77.67±5.61 vs 10.33±0.82, (106.80±11.91) pg/ml vs (82.45±19.80) pg/ml, t value was 19.471, 34.848, 2.542, respectively, all P<0.05). Compared with the control group, the ratio of Treg cell increased in basal sensitization group but decreased in OVA/AR group ((10.29±0.47)% vs (9.28±0.16)%, (8.49±0.15)% vs (9.28±0.16)%, t value was 5.838, 4.540, respectively, all P<0.01). Compared with control group, the expression of Notch1 increased significantly both in basal sensitization group and OVA/AR group (1.04±0.05 vs 0.71±0.05, 1.83±0.10 vs 0.71±0.05, t value was 9.293, 31.363, respectively, all P<0.01); and the expression of Jagged1 only increased significantly in OVA/AR group (0.41±0.04 vs 0.21±0.01, t=13.472, P<0.01). It was found that Notch1 was positively correlated with the level of IL-6, IL-10 by Pearson test (r value was 0.98, 0.87, respectively, all P<0.01). Compared with control volunteers, the expression of Notch1 and Jagged1 increased significantly in AR group patients ((1 135.0±254.9) pg/ml vs (436.0±139.3) pg/ml, (1 200.2±401.0) pg/ml vs (559.9±124.2) pg/ml, t value was 13.99, 11.94, respectively, all P<0.01).@*Conclusions@#The expression of Notch1 receptor and ligand increased significantly in the pathogenesis of AR. Notch1-Jagged1 may promote the occurrence and development of AR by up-regulating the expression of IL-6 and IL-10.