Role Of CD23 In The Pathogenesis Of Eosinophilic Chronic Rhinosinusitis With Nasal Polyps

BackgroundAllergic rhinitis(AR)and nasal polyps(NPs)are common diseases in the department of otolaryngology.Allergic rhinitis was previously considered to be a disease confined to the nasal cavity.Now it is considered a systemic airway disease.AR is a kind of nasal congestion,nasal itching,runny nose,swelling of the nasal mucosa,etc.,which is triggered by allergens,mediated by Immunoglobulin E(IgE),and participates in multiple immune cells and immune factors Manifestations of type? allergic disease.According to statistics,the global average incidence of AR is 10%to 40%.In recent years,with the global environmental,scientific and technological,economic,industrial development,and air pollution,the incidence of AR has also increased year by year.Increasingly becoming a global health issue.Nasal polyps are a new type of organism that occurs on the surface of the nasal cavity and sinuses,which are smooth,translucent,and shaped like lychee meat.They are often secondary to AR.Recent studies have shown that eosinophil(EOS),IgE,Mast cells(MC),T lymphocytes,cytokines,chemokines,Tumor necrosis factor-?(TNF-?),and interferon are more abundant than normal tissues.Some studies have suggested that the increase in eosinophils in nasal polyp tissue can lead to allergic reactions,and the mechanism may be due to the localized type I allergic reaction mediated by specific IgE after nasal mucosa contact with the allergen,causing MC to degranulate and release a series of inflammatory mediators and chemokines,leading to a large amount of leukotrienes(LTs),histamine,EOS,etc.,a large number of EOS can release inflammatory mediators,such as eosinophil(eosinophil cation protein(ECP)and major basic proteins(MBP),etc.,and then damage the nasal mucosal epithelial cells to form tissue edema.Repeated nasal mucosal damage and edema can lead to the formation of nasal polyps.Studies have shown that human nasal mucosal epithelial cells express the low-affinity receptor Fc?R ?(CD23)of IgE,which can participate in the two-way transport of IgE and the transport of IgE immune complexes through the nasal mucosal epithelial cell barrier,initiating allergic rhinitis and recruiting Eosinophils,T lymphocytes,and neutrophils are further involved in the further development of allergic rhinitis.Whether this mechanism exists in eosinophilic chronic rhinosinusitis with nasal polyps needs to be further explored.ObjectiveThe purpose of this study was to investigate the expression of CD23 in mucosal tissues of patients in eosinophilic chronic rhinosinusitis with nasal polyps,and whether CD23 participates in and mediates the occurrence of eosinophilic chronic rhinosinusitis with nasal polyps,and to detect CD23,ERK,CCL20 and the expression of IL-8 in eosinophilic chronic rhinosinusitis with nasal polyps and its correlation,and to explore new targets for the treatment of eosinophilic chronic rhinosinusitis with nasal polyps.Materials and MethodThirty-four patients with nasal polypectomy who underwent nasal endoscopic nasal polypectomy in the nasal department of our hospital from January 2019 to October 10,2019 were collected as specimens,and hematoxylin-eosin staining(HE)was performed in parallel,high power Observe the degree of eosinophil infiltration in nasal polyps and count under high-power field(HPF).Determine eosinophilic chronic rhinosinusitis with nasal polyps,taking eosinophils>70/HPF as Eos-CRSwNP(eosinophilic chronic rhinosinusitis with nasal polyps,Eos-CRSwNP),taking eosinophils<70/HPF as nonEos-CRSwNP(noneosinophilic chronic rhinosinusitis with nasal polyps,nonEos-CRSwNP)as the standard,patients with nasal polyps were divided into Eos-CRswNP group and nonEos-CRSwNP group.Patients who underwent nasal endoscopic nasal skull base benign mass resection and/or cerebrospinal fluid rhinorrhea(normal control group)had the inferior turbinate mucosa tissue taken during the operation as a specimen.The diagnosis of patients with nasal polyps was based on the 2012 guidelines for the diagnosis and treatment of chronic rhinosinusitis developed by the rhinology group of the Otolaryngology Head and Neck Surgery Branch of the Chinese Medical Association in 2012.Hematoxylin-eosin(HE)was used to measure the expression of inflammatory cells such as EOS and histological changes in the nasal mucosa.Enzyme-linked immunosorbent assay(ELISA)was used to detect human serum.Total IgE,ECP,Leukotriene C4(LTC4),Interleukin-4(IL-4),Interleukin-10(IL-10)levels,and nasal lavage fluid LTC4,IgE expression levels;the expression of CD23 in each tissue was detected by immunohistochemistry(SP method)and Western Blot;correlation analysis was used to analyze the correlation between p-ERK levels and CD23 expression in nasal lavage Correlation between CCL20 level,IL-8 level and p-ERK level,CCL20 level,IL-8 level and eosinophil count,and Correlationt between the expression of CD23 and EOS infiltration,ECP and LTC4 level.ResultThe HE staining results showed that compared with the normal control group,in the Eos-CRSwNP group,the epithelial cells were thickened,the edema was seen in the stroma,the arteriovenous hyperplasia was not obvious,the basement membrane was significantly damaged,and a large amount was seen in the epithelium and stroma infiltration of inflammatory cells,mainly infiltration of eosinophils;in the nonEos-CRSwNP group,epithelial cell hyperplasia and thickening,obvious edema in the interstitial space,large cysts retained under the mucosa,obvious gland blockage,pus cysts,and some basement membranes When damaged,inflammatory cell infiltration can be seen in the epithelial layer and interstitial,mainly neutrophil and lymphocyte infiltration,and eosinophil infiltration is relatively rare.Eosinophil count under high power microscope showed:Eos-CRSwNP group(93.47±27.11),nonEos-CRSwNP group(2.36±1.31),blank control group(normal)(0.85±0.76),eosinophils The degree of infiltration in the Eos-CRSwNP group was significantly higher than that in the nonEos-CRSwNP group and the blank control group,and the difference was statistically significant(P<0.05).ELISA test results showed that serum-specific IgE,IL-4,ECP,and LTC4 levels in the Eos-CRSwNP group were significantly higher than those in the nonEos-CRSwNP group and the blank control group,and the difference was statistically significant(P<0.05).The level of IL-4 was higher than that of the blank control group,and the difference was statistically significant(P<0.05).There was no significant difference in serum specific IgE,ECP,LTC4 levels between the nonEos-CRSwNP group and the blank control group(P>0.05).Immunohistochemical results showed that in the Eos-CRSwNP group,CD23 expression was mainly in epithelial cells,and a small amount was also expressed in mucosal gland epithelial cells and submucosal immune cells.The positive expression was brown or brownish yellow,mainly distributed on the top surface of the cells.In the cell membrane and cytoplasm of the basal plane;in the nonEos-CRSwNP group and the blank control group,a small amount of CD23 expression was seen in the epithelial cells,and the inflammatory expression was light yellow-brown.Western Blot test results showed that in Eos-CRSwNP mucosal tissue,there were obvious CD23,p-ERK,CCL20,and IL-8 immunoreactive bands at 40kDa,42kDa,11 kDa,8 kDa,nonEos-CRSwNP group and blank control group the immune response bands were significantly weaker than those in the Eos-CRSwNP group;Image J software was used to semi-quantitatively analyze the band gray values of the immune response bands.The gray value was significantly higher than the nonEos-CRSwNP group and the blank control group,and the difference was statistically significant(P<0.05).There was no significant difference between the nonEos-CRSwNP group and the blank control group,and the difference was not statistically significant(P>0.05);Pearson's correlation test showed that eosinophil counts,ECP levels,serum LTC4 levels in serum and CD23 expression were positively correlated with CD23 expression in the Eos-CRSwNP group(r=0.76,r=0.69,r=0.73,P<0.05),The level of p-ERK was positively correlated with the expression of CD23(r=0.77,P<0.05),and the levels of CCL20 and IL-8 were positively correlated with the level of p-ERK(r=0.77,r=0.72,P<0.05);acidophilic Granulocyte count was positively correlated with CCL20 and IL-8 levels(r=0.71,r=0.82,P<0.05).Conclusion(1)CD23 is structurally expressed in human nasal mucosa tissue,and CD 23 expression is up-regulated in mucosal tissue of patients with eosinophilic chronic rhinosinusitis with nasal polyps;(2)In patients with eosinophilic chronic rhinosinusitis with nasal polyps,CD23 may trigger the allergic inflammatory response by mediating the transepithelial transport of IgE and CD23-IgE allergen complexes;(3)CD23 is activated through the ERK signaling pathway and participates in the recruitment and activation of eosinophils with eosinophilic chronic rhinosinusitis with nasal polyps,which is expected to become a new target for the treatment of eosinophilic chronic rhinosinusitis with nasal polyps.