Targeting the CD74-MHC II axis with allergen-specific immunotherapy ameliorates pollen-induced allergic asthma

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.