[The expression of Notch pathway in nasal polyps and its correlation with the decreased Treg percentage and...

Objective: To investigate the correlation between Notch pathway expression in nasal polyps and Treg percentage and Eos infiltration. Methods: Patients with chronic sinusitis and simple nasal septum deviation who received nasal endoscopic surgery in the Third Affiliated Hospital of Sun Yat-Sen University between November 2012 and August 2018 were selected and enrolled in CRS group and control group respectively. Nasal mucosa tissues were collected from 30 CRSsNP patients (14 males and 16 females aged from 18 to 63), 58 CRSwNP patients (38 males and 20 females aged from 18 to 65) and 29 patients (19 males and 10 females aged from 20 to 57), who underwent nasal endoscopic surgery for correction of simple nasal septum deviation. Hematoxylin-eosin(HE) staining was used to observe the infiltration of eosinophilic granulocytes in the tissues and to classify chronic sinusitis with polyps (CRSwNP) into eosinophilic chronic rhinosinusitis with nasal polyps (Eos-CRSwNP)and non-eosinophilic chronic rhinosinusitis with nasal polyps (Eos-CRSwNP). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of Notch pathway receptors (Notch-l, 2, 3, 4) and their ligands (Jagded-l, Jagded-2, Delta-l, Delta-3and Delta-4) in the nasal mucosa of each group, as well as the expression of Th2 cytokines (IL-4, IL-5, IL-13), eosinophilic cationic protein (ECP)and the key transcription factor Foxp3 in Treg cells. Finally, flow cytometry was used to detect CD4⁺CD25⁺Foxp3⁺ Treg cells in nasal mucosa of each group. Results: Compared with controls, the expression of Th2 cytokines (IL-4, IL-5, IL-13) in CRSsNP and non-Eos-CRSwNP patients was the highest in Eos-CRSwNP (F=16.930,9.197,9.116, all P<0.05). Foxp3 had the lowest expression in Eos-CRSwNP patients and was lower than non-Eos-CRSwNP patients (F=2.780,P<0.05), and was negatively correlated with ECP (r=-0.326,P<0.05). Compared with controls, Eos-CRSwNP patients in CRSsNP patients and non-Eos-CRSwNP patients exhibited a significantly lower frequency of CD4⁺CD25⁺Foxp3⁺Treg cells (F=13.140, all P<0.01). The expression of Notch-l and Jagged-l in Eos-CRSwNP was significantly higher than that of the controls, CRSsNP patients and non-Eos-CRSwNP patients (F=5.953/F=6.380, P<0.05). In the nasal polyp group, the expression of Notch-l and Jagged-l showed significantly negative correlation with Foxp3 (r=-0.611/-0.346, all P<0.05), and positive correlation with Th2 cytokines (IL-4, IL-5, IL-13) and ECP, respectively (r=0.781/0.459,0.621/0.601,0.605/0.490,0.464/0.668, all P<0.05). There was no significant difference in the expression of receptor and ligand of the other Notch pathway among the groups. Conclusion: Abnormal activation of Notch-l/Jagged-l pathway may be involved in decreasing Treg ratio in Eos-CRSwNP, thereby promoting Th2 inflammatory response and Eosinophil infiltration.