| Allergic rhinitis is generally considered to be a nasal mucosal allergic disease mediated by various inflammatory cytokines(e.g.,IL-4 and IL-5)and Ig E mediated by the entry of inhaled allergens into the nasal mucosa of sensitized individuals,resulting in the degranulation of mast cells.At present,it is believed that among numerous pathogenic factors,Th1/Th2 immune imbalance played a dominant role in the pathogenesis of AR,whose immunopathology is characterized by the infiltration of nasal mucosal tissues expressing a large number of Th2 cytokines(IL-4,IL-5,IL-13).It has been found that there is a heterogeneous innate lymphoid cell population in airway mucosal tissues,and it is believed that the group 2 innate lymphoid cells which can produce IL-5 and IL-13 may be the source of early Th2 cytokines and effector cells that initiate the immune response of Th2 cells.Activation of ILC2 s secretes a large amount of type 2 cytokines,which can promote the proliferation of eosinophils,promote the differentiation of epithelial cells,and induce high secretion of mucus.In the early stage of allergic rhinitis,the proliferation and activation of ILC2 s is an important factor promoting the development of allergic reaction.Autophagy is a cellular degradation pathway that maintains a relatively low basal autophagy level in cells under normal physiological conditions,and is rapidly upregulated when cells are under stress.The role of autophagy in AR is still being explored,and it has been found that autophagy can participate in AR process from airway response,immune response and chronic inflammatory response.Nasal epithelial cells are the first line of defense against foreign pathogens.In AR patients,the level of autophagy in nasal epithelial cells is up-regulated,and they express high levels of autophagosomes and autophagy markers(microtubule-associated protein 1 light chain 3 beta,LC3),which are associated with airway remodeling.In studies on allergic diseases,it has been found that lack of autophagy can reduce the secretion of cytokines(IL-5,IL-13,etc.)of activated ILC2 s,and the overexpression of autophagy can promote the activation and proliferation of ILC2 s.ObjectiveIn this study,the mouse model of allergic rhinitis was established,and sampling time was set during the modeling process to take samples periodically.The contents of IL-4,IL-5 and s Ig E in serum of mice in each group were analyzed,the proportion of type 2innate lymphoid cells in lymphocytes in spleen of each group was compared,and the expression of epithelial autophagy markers in nasal mucosa of each group was analyzed.The purpose of this study was to investigate the secretion of IL-5 and autophagy by type2 innate lymphocytes in the early stage of allergic rhinitis.To investigate the expression of ILC2 s and LC3 in the pathogenesis of allergic rhinitis.Methods Seventy BALC/C mice aged 49-55 days were randomly divided into experimental group and control group.In the experimental group,dust mites and aluminum hydroxide adjuvant were used for AR modeling.Mice in the experimental group were sacrificed on days 1,8,15,22,25 and 28 and labeled as the experimental group 1-6.The control group was given PBS and sacrificed on day 28 and marked as the control group.The eye blood,nasal mucosa and spleen of mice in each group were collected,and the contents of IL-4,IL-5 and dust mite specific Ig E in serum were detected by ELISA.The percentage of ILC2 s in lymphocytes in spleen was detected by flow cytometry.The morphological changes of nasal mucosa were detected by HE staining,and the expression of LC3 in nasal mucosa was detected by immunohistochemical staining.Use Grap Pad Prism8.0.1 software to analyze data,using single factor analysis of variance is compared between groups,two two compared the LSD-t test.Results1.Comparison of behavioral results between the experimental group and the control group: compared with the control group,the symptoms of sneezing,rubbing nose and runny nose in the experimental group were obvious,with statistical significance(P<0.05).2.Comparison of hematoxylin-eosin staining results of nasal mucosal tissues of mice in the experimental group and the control group: Under microscope,epithelial tissues in the control group were neatly arranged without glandular hyperplasia and inflammatory cell infiltration;In the experimental group,the epithelium was significantly thickened,the epithelial cells were arranged in disorder,the basement membrane was thickened,the glands were increased,and the lymphocyte infiltration was obvious,which further proved the success of constructing the allergic rhinitis model.3.Comparison of serum IL-5 expression between experimental group and control group: the serum IL-5 content in experimental group 5 and 6 was significantly higher than that in control group(P<0.05);There was no significant difference in serum IL-5content between experimental group 3 and 5 and experimental group 6(P>0.05).4.Comparison of serum IL-4 expression between experimental group and control group: The serum IL-4 content of experimental group 5 and 6 was significantly higher than that of control group(P<0.05).5.Comparison of serum dust mite specific Ig E expression between experimental group and control group: the serum dust mite specific Ig E content in experimental group4,5 and 6 was significantly higher than that in control group,with significant difference(P<0.05).6.Expression of autophagy marker LC3 in nasal mucosa of mice in each experimental group and control group: Under microscope,brown staining(LC3expression)in the upper cortex of each experimental group was different,while that in the control group was lighter.The average optical density value of the experimental group was compared with that of the control group: the average optical density value of the control group represented the basic autophagy level;the change of the average optical density value of the experimental group increased first and then decreased with the increase of the number of doses,indicating the change of the autophagy level from low to high(higher than the basic level),and then decreased to the basic autophagy level.7.Compared with the control group,the proportion of ILC2 s in total lymphocyte count in spleen of mice in experimental groups increased first and then decreased with the increase of times of administration,and was still higher than that in the control group until the end of the whole time of modeling.Conclusion1.ILC2 s may be the first immune molecule activated in the disease progression of allergic rhinitis mice,which increases in the early stage of the disease and then decreases as the disease progresses.2.ILC2 s may induce and promote Th2 type cellular immune response by secreting IL-5.3.In the early stage of allergic rhinitis mice,IL-5 may promote the secretion of IL-4 by eosinophils and cooperate with IL-4 to stimulate the production of specific Ig E by B cells.4.The level of autophagy in mice with allergic rhinitis increased at the early stage of the disease,and then decreased with the progression of the disease,which was time-correlated with the change of ILC2 s.Autophagy may play a role in promoting the development of inflammation in the process of AR. |
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