[CGRP inhibits proliferation, activation and cytokine secretion of group 2 innate lymphoid cells (ILC2) in peripheral blood from patients with allergic rhinitis].

Objective To investigate the effect of calcitonin gene-related peptide (CGRP) on the regulation of group 2 innate lymphoid cells (ILC2) in the peripheral blood of patients with allergic rhinitis (AR). Methods Peripheral blood mononuclear cells (PBMCs) were extracted from normal healthy individuals and AR patients, then stimulated with CGRP, interleukin 33 (IL-33) and CGRP combined with IL-33 for 3 days, with blank stimulus as control. The percentage of ILC2 in the four groups was measured by flow cytometry. After being sorted, ILC2 was given to CGRP, IL-33 and CGRP combined with IL-33 stimulation for 3 days, with blank stimulus as control. The percentage of IL-5 and IL-13 positive cells in ILC2 was detected by flow cytometry, and the levels of IL-5 and IL-13 in ILC2 supernatant were measured by ELISA. Results The percentage of ILC2 in the peripheral blood of AR patients was significantly higher than that of the control group. The levels of IL-5+ILC2 and IL-13+ILC2 were significantly increased by IL-33 single stimulation after culturing PBMCs. After adding IL-33 combined with CGRP stimulation, the levels of IL-5+ILC2 and IL-13+ILC2 in PBMCs were significantly reduced; after CGRP single stimulation, the levels of IL-5+ILC2 and IL-13+ILC2 in PBMCs were further decreased. After ILC2 was sorted and cultured, the levels of IL-5+ILC2 and IL-13+ILC2 showed significant increase after IL-33 single stimulation. The levels of IL-5+ILC2 and IL-13+ILC2 were decreased by IL-33 and CGRP co-stimulation, and they were further reduced after CGRP single stimulation. Compared to IL-33 single stimulation, IL-5 and IL-13 levels dropped significantly due to the IL-33 and CGRP co-stimulation. The levels of IL-5 and IL-13 were further reduced by CGRP single stimulation. Conclusion CGRP inhibits the proliferation and activation of peripheral blood ILC2 in AR and exert anti-inflammatory effects in AR.

Neuromedin U Induces Activation of Peripheral Group 2 Innate Lymphoid Cells through the ERK Pathway in Allergic Rhinitis Patients.

INTRODUCTION: In allergic diseases, group 2 innate lymphoid cells (ILC2s) play critical roles. Neuromedin U (NMU), a highly conserved multifunctional neuropeptide, is secreted by cholinergic neurons and involved in asthma pathogenesis by amplifying lung inflammation driven by ILC2s. However, the precise effects of NMU on ILC2s in allergic rhinitis (AR) and related diseases remain unclear. METHODS: A total of 15 patients with persistent AR and 8 healthy controls (HCs) were enrolled in the study. Visual analog scale (VAS) scores are used to assess the severity of clinical symptoms in AR patients. The percentages of ILC2s in peripheral blood mononuclear cells (PBMCs) were enumerated using flow cytometry. The soluble or intracellular cytokines (IL-5 and IL-13) in PBMCs or sorted ILC2s were assessed in response to various stimuli with IL-33, NMU, IL-33 combined with extracellular signal-related kinase (ERK) inhibitor or NMU combined with ERK inhibitor in the presence of IL-2. RESULTS: We confirmed the proportion of circulating ILC2s was significantly higher in AR patients than in HCs. ILC2s levels were found to be positively related to VAS scores. We also discovered that the release of IL-5 and IL-13 in AR patients' PBMCs stimulated by NMU (p < 0.0001 and p < 0.0001, respectively) or IL-33 (p = 0.002; p = 0.044, respectively) was significantly higher than in HCs. In AR patients, NMU stimulated PBMCs or ILC2s to generate greater inflammatory factors IL-5 and IL-13 compared to IL-33. Furthermore, we observed that NMU-promoted ILC2s activation and proliferation functions were restricted when the ERK pathway was inhibited. CONCLUSION: NMU effectively activated ILC2s in AR patients to produce Th2-type cytokines, and this activation can be prevented by ERK pathway inhibitors. Our findings shed new light on the neuro-immune mechanism of AR and offer new insights into its prevention and treatment.

Clinical Efficacy of Single Vidian Neurectomy in Chronic Rhinosinusitis with Nasal Polyps and Allergic Rhinitis.

OBJECTIVE: To investigate the clinical efficacy of single Vidian neurectomy (sVN) in the treatment of chronic rhinosinusitis with nasal polyps and allergic rhinitis (CRSwNP &AR). STUDY DESIGN: Descriptive study.   Place and Duration of Study: Otolaryngology-Head &Neck Surgery, Shanxi Medical University Second Affiliated Hospital, Taiyuan, China, February 2016 to February 2019. METHODOLOGY: Patients meeting the diagnostic criteria for AR and CRSwNP confirmed after assessment by an ENT physician; moderately severe and persistent AR, aged ≥18 years to ≤70 years; and testing positive for sIgE and were regularly treated with medications for three months or more before surgery with unsatisfactory symptom control. Exclusion criteria were patients with acute exacerbations of sinusitis or fungal sinusitis combined with nasal polyps, intolerant to aspirin, acute infection or sinus tumours; contraindications to general anaesthetic surgery or oral corticosteroids; and those who have received allergen immunotherapy, corticosteroids and antihistamines within one year. The relevant epidemiological data were collected, including IgE level, VAS, RQLQ, and the Lund-Kennedy scores, to assess patients' clinical symptoms and quality of life before and after surgery. RESULTS: Fifty-five patients were followed up for two years after surgery, and statistical analysis was performed using SPSS version 25.0. It was found that VAS scores, RQLQ scores, and Lund-Kennedy scores of the patients who underwent sVN were significantly lower at six months (all p <0.01), one year (all p <0.01, and two years all p <0.01) after surgery compared with those before surgery. CONCLUSION: sVN has better efficacy in patients with CRSwNP&AR, has the potential to reduce its recurrence rate, and seems to be a safe and effective treatment. KEY WORDS: Chronic rhinosinusitis with nasal polyps, Allergic rhinitis, Eosinophilic chronic rhinosinusitis with nasal polyps, Single Vidian neurectomy, Clinical efficacy.