Background The incidence and prevalence of allergic asthma are increasing year by year, making it one of the major public health concerns affecting human health. Artemisia annua (A. annua) pollen is a key allergen responsible for allergic asthma in northern China. Allergen-specific immunotherapy (AIT), including subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT), is an important strategy for the treatment of allergic diseases. The aim of this study was to investigate the effect of A. annua allergen-specific immunotherapy (AIT) on allergic asthma and its potential mechanism. Methods An Artemisia annua-induced allergic asthma mouse model was established by subcutaneous sensitization plus aerosol challenge. Methacholine challenge, Wright–Giemsa, H&E and AB–PAS staining were used to validate the model and assess specific immunotherapy efficacy. Inflammatory factors in bronchoalveolar lavage fluid (BALF) and lung tissues were detected via ELISA and high-throughput Luminex assay. Proteomic analysis explored the potential mechanism of SCIT, with results verified by Western blot and immunofluorescence. Our preclinical data identified CD74-enriched immune cell subsets in human peripheral blood mononuclear cells (PBMCs) by using Flow cytometry. Results Compared with the control group, asthmatic mice exhibited significantly increased airway hyperresponsiveness, serum IgE, IgG1 and IgG2a levels, BALF inflammatory cell counts, IL-1β and TNF-α secretion, as well as severe peribronchial inflammatory infiltration. Lung tissue expression of IL-5, IL-3, CCL2 and TNF-α was also markedly elevated. Notably, SCIT treatment significantly ameliorated these abnormalities except for serum total IgE, IgG1 and IgG2a. Moreover, SCIT inhibited the asthma-induced upregulation of CD74, MHC-II, CD11c and GATA3, and significantly increased FOXP3 expression.Consistently, flow cytometric analysis of human peripheral blood mononuclear cells (PBMCs) revealed elevated CD74-MHC-II axis expression on plasmacytoid dendritic cells (pDCs) in asthmatic participants, with a prominent downward tendency observed following SLIT treatment. Conclusions In conclusion, Artemisia annua pollen-specific immunotherapy alleviates airway inflammation and hyperresponsiveness in allergic asthma and attenuated GATA3-related type 2 inflammation, possibly in association with inhibition of CD74-MHC-II axis activation within plasmacytoid dendritic cells.
Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by pronounced epithelial remodeling and barrier dysfunction, contributing to a high rate of postoperative recurrence. However, molecular mechanisms associated with early recurrence remain poorly understood. Methods We performed paired proteomic profiling of nasal polyp tissues obtained from the same patients before initial surgery and at the time of recurrence (discovery cohort) to identify recurrence-associated proteins. Candidate proteins were validated in an independent cohort, and their association with recurrence risk was assessed by receiver operating characteristic (ROC) curve and Kaplan-Meier analyses. The expression and cellular localization of the identified candidate were further characterized by immunofluorescence. Mechanistic investigations were conducted in primary human nasal epithelial cells using ATP stimulation and specific pharmacological inhibitors. Results Paired proteomic analysis identified P2X7, PDE4D, and JADE2 as the top 3 upregulated proteins in recurrent tissues. Among these, only P2X7 was consistently elevated in the validation cohort and predominantly localized to the nasal epithelium (P < 0.01). ROC curve analysis indicated that tissue P2X7 level might serve as a potential predictive marker for postoperative recurrence of CRSwNP. (AUC = 0.678, P = 0.022). Kaplan-Meier analysis further showed that the risk of recurrence was significantly higher in the high P2X7 expression group (HR = 2.323, P = 0.015). Recurrent tissues exhibited elevated levels of NLRP3 and IL-1β, reduced expression of epithelial barrier markers occludin and E-cadherin, accompanied by increased extracellular ATP concentrations. In vitro, ATP stimulation upregulated P2X7 expression, induced NLRP3 and cleaved IL-1β, and downregulated occludin and E-cadherin. Notably, these effects were reversed by a P2X7-specific inhibitor (A-438079). Conclusion Paired proteomic profiling revealed distinct protein expression profiles between pre- and post-recurrence nasal polyps, with P2X7 serving as a promising predictive biomarker for early recurrence. Mechanistically, the ATP/P2X7 axis may drive disease recurrence by potentially promoting inflammasome activation and epithelial barrier disruption.
