The Inhibition Of IFN-? On Acute Allergic Airway Inflammation In Mice

Background Acute allergic airway inflammation is the pathophysiological basis of allergic asthma,caused by an inappropriate immune response to excessive stimulation.Although asthma is long thought to be driven by allergen-reactive Th2 cells.A very exciting recent development is the discovery of innate lymphoid cells(ILCs)as key players in the pathogenesis of asthma.Group 2 innate lymphoid cells(ILC2s)are present in mesenteric fat-associated lymphoid clusters and non-lymphoid tissues,including the lung,liver,skin,intestine and visceral adipose tissue.ILC2 s can be activated by epithelial-derived cytokines,including thymic stromal lymphopoietin(TSLP),IL-33 and IL-25.IL-33 is a member of the IL-1 family and ST2 receptors is expressed on the surface of the ILC2 s.IL-33 can attach to the ST2-IL-1 receptor helper protein complex which expressed on the surface of ILC2 s,resulting in the activation of ILC2 s and the secretion of a large number of Th2 cytokines such as IL-5,IL-13.IL-5 is associated with eosinophil accumulation and the exacerbation of inflammatory responses;IL-13 can promotes goblet cell mucus secretion and smooth muscle contraction.Naive CD4 ~+ T(Th0)cells differentiate into Th1 or Th2 cells,and type 1 and type 2 cytokines cross-regulate Th2 and Th1 development and expansion.Interferon-?(IFN-?),a type 1 cytokine secreted by Th1 cells,CD8 ~+ effector T cells,NK cells,NKT cells and other cells in response to acute inflammation or viral infection,is a key regulator that initiates type 1 immune responses while suppressing type 2 immunity.However,the effect of IFN-? on ILC2 has not been properly evaluated.Given that ILC2 s are the mirror image cells of Th2 cells,we hypothesize that IFN-? may have an inhibitory effect on ILC2 s.Objective In this study we established a acute allergic airway inflammation model of C57BL/6 mice which were induced by IL-33,and then interfered the acute allergic airway inflammation mice with IFN-? to investigate the inhibitory mechanism of IFN-? on acute allergic airway inflammation and it's effects on the production of IL-5 and IL-13.This paper will provide experimental data for treating acute allergic airway inflammation in clinic.Materials and methods Twenty-four female(6-8 weeks)C57BL/6 mice were randomly divided into four groups: IL-33 model group,IFN-? group,PBS control group,IL-33 plus IFN-? group,those groups were treat with 40 ?l cytokines in PBS or PBS alone through intranasal on day 0 and 3.Executed them on day 6 and collected bronchial alveolar lavage fluid(BALF)and lung tissues.We observed the pathological changes by hematoxylin and eosin(HE)and periodic acid-Schiff reagent(PAS)staining,analyzed Group 2 innate lymphoid cells(ILC2s)and eosinophils by flow cytometry,measued the levels of IL-5 and IL-13 in the supernatant of lung homogenate and BALF by ELISA,detected the levels of IL-5?IL-13 and ST2 m RNA by Real-time PCR.Results1.Pathological changes Compared with the PBS control group,IL-33 group had more inflammatory cells infiltration,mucus secretion and hyperplasia of goblet cells in bronchial mucosa;Compared with the IL-33 group,IL-33 plus IFN-? group had less inflammatory cells infiltration,mucus secretion and hyperplasia of goblet cells in bronchial mucosa.2.Flow cytometry results Compared with the PBS control group,IL-33 group had more eosnophils and ILC2 s in lung tissue and BALF(p<0.05);Compared with the IL-33 group,L-33 plus IFN-? group had less eosnophils and ILC2 s in lung tissue and BALF(p<0.05).3.ELISA results Compared with the PBS control group,the levels of IL-5,IL-13 in lung tissue homogenate and BALF were increased in IL-33 group(p<0.05);Compar-ed with the IL-33 group,the levels of IL-5,IL-13 in lung tissue homogenate and BALF were decreaced in L-33 plus IFN-? group(p<0.05).4.Real-time PCR results Compared with the PBS control group,the expression of IL-5,IL-13,ST2 at m RNA level were increased in IL-33 group(p<0.05);Compared with the IL-33 group,the expression of IL-5,IL-13,ST2 at m RNA level were decreased in IL-33 plus IFN-? group(p<0.05).Conclusion1.IL-33 can successfully induce acute allergic airway inflammation model.2.IFN-? can reduce the number of ILC2 s and the levels of IL-5,IL-13 in lung tiss-ues and BALF,which can alleviate the acute allergic airway inflammation.