The Significance Of Type 2 Innate Lymphoid Cell In Airway Inflamation Of Non-allergic Asthmatics

BackgroundAsthma is a heterogeneous disease with various pathobiologic processes and phenotypied by multiple different approaches.Based on the trigger exposure,asthma generally can be classified as allergic and non-allergic.Allergic asthma results from allergen-induced type 2 inflammation typically companied with increased eosinophils.Even though independence from allergen exposure and sensitization,non-allergic asthma,caused by environmental factors such as air pollutants,viral or bacterial infections and obesity,sometimes was related to type 2 inflammation response and high level of eosinophils too.We have know that the inflammation process of allergic asthma which leads to elevated eosinophils,airway hyperactivity(AHR)and mucus production depending on T helper 2(Th2)cells and type 2 innate lymphoid cells(ILC2s).However,much remains to be uncovered in non-allergic asthma.It was reported that ILC2 might be the source of type 2 cytokines and associated with increased eosinophils in non-allergic asthma,but little direct clinical evidence was given.Glucocorticoid is still the most common therapy to asthmatics,which generally works well on the allergic asthma but the non-allergic type is resistant to.Studies showed ILC2s were refractory to glucocorticoid.Understanding whether the ILC2s play a potential novel role in the underlying mechanisms of non-allergic asthma will help developing new and targeted therapies applicable to this disease.ObjectiveCurrently,the majority of studies on ILC2s in the lung have concentrated on their role in allergic diseases,but little related to their function in the non-allergic forms.We will detect whether ILC2-mediated innate immunity is involved in non-allergic asthma and its association with type 2 cytokines and eosinophils in the non-allergic phenotype.That will help developing new and specific therapies applicable to this disease.MethodsIn our study,47 patients with asthma were recruited in the Department of Respiratory,Qilu Hospital of Shandong University,and 15 healthy donors were recruited serving as controls(2018.11-2019.9).We collected the clinical date of patients including age,sex,BMI.Routine blood for peripheral blood eosinophil counts were conducted by the clinical laboratory of Qilu hospital.Patients" peripheral blood was collected to measure the the levels of ILC2 by flow cytometry.Serum was isolated from the peripheral blood used for the test of slgE through phadiatop test;plasma was isolated from the peripheral blood used for testing tIgE levels and the concentrations of type 2 cytokines with ELISA kits.Lung function test was also performed for every patient.According to sIgE and blood eosinophil counts,asthmatic patients were divided into four groups:allergic eosinophilic asthmatics,allergic non-eosinophilic asthmatics,non-allergic eosinophilic asthmatics and non-allergic non-eosinophilic asthmatics.We compared the levels of ILC2 and type 2 cytokines among different groups and performed correlation analysis of ILC2 and peripheral blood eosinophil with their related factors.All data was analyzed by SPSS software(version 23).ResultsThe levels of ILC2 in the non-allergic eosinophilic asthmatics were higher than that of healthy controls and the non-allergic non-eosinophilic asthmatics.There was no statistically difference between the ILC2 level of allergic eosinophilic asthmtics and that of the non-allergic eosinophilic asthmtic patients.IL-5 was increased in the patients with non-allergic eosinophilic asthma compared to the healthy controls and non-allergic non-eosinophilic asthmtics.The IL-5 level of allergic eosinophilic asthmtic patients was not higher compared to that of the non-allergic eosinophilic asthmtic patients.IL-13 level of the patients with non-allergic eosinophilic asthma was all significantly greater than the healthy controls.Pearson correlation analysis showed that ILC2 level was positively correlated with the eosinophil counts(r=0.653,p=0.008),IL-5 concentration(r=0.622,p=0.013)and IL-13 concentration(r=0.522,p=0.046)in non-allergic eosinophilic asthmatics.Spearman correlation analysis showed there was no strong correlation between ILC2 level and slgE concentration in allergic eosinophilic asthmatics(r=0.125,p=0.676).Pearson correlation analysis showed the blood eosinophil counts was positively correlated with IL-5 level(r=0.591,p=0.02)but not related to IL-13 level(r=0.423,p=0.1 17)in non-allergic eosinophilic asthmaticsConclusionsIn summary,ILC2s maybe play a important role in non-allergic asthmatics and associated the production of type 2 inflammation cytokines(IL-5,IL-13)and the blood eosinophils.