Sublingual immunotherapy suppresses Th2-type immune response in the allergic rhinitis mouse model by inhibiting the activation of the NFκB pathway
Year: 2025
Type: article
Abstract: AIMS: Allergic rhinitis (AR) is an IgE-mediated response to aeroallergens. Sublingual immunotherapy (SLIT) alleviates AR by suppressing Th2 responses. This study investigates the mechanism underlying SLIT-mediated Th2 suppression in AR treatment. MATERIALS & METHODS: An AR mouse model was established by intraperitoneal injection of alum-adsorbed Phleum pratense extract in BALB/c mice. SLIT efficacy were assessed by evaluating clinical symptoms, IgE levels, splenic and cervical lymph node (cLN) cell proliferation, cytokine profiles, and proportion of Th17 and Treg cells. Mechanisms were explored using bioinformatics analysis and Western blotting. RESULTS: AR mice displayed increased sneezing, nasal lavage IgE, and eosinophilia. Spleen cell proliferation remained unchanged, while cLN proliferation was elevated. SLIT reversed elevated IL-4/IL-5, Th17, and reduced IFN-γ/Treg levels in both spleen and cLN. Microarray analysis of GSE206149 revealed NFκB pathway enrichment in SLIT-treated AR patients. SLIT inhibited NFκB activation (reduced p-IκBα/p-NFκB p65) in AR mice. The NFκB inhibitor BAY11-7082 amplified SLIT's therapeutic effects, further suppressing Th2 responses. Conversely, IκBα knockdown abolished SLIT's benefits, confirming NFκB's essential role. CONCLUSION: Collectively, we demonstrated that SLIT inhibits NFκB pathway activation, thereby suppressing the Th2-type immune response and alleviating AR progression. These findings provide new insights into the mechanism of SLIT in the treatment of AR.
Source: Immunotherapy
Authors: Gan Wang, Zhiling Chen
Institution: Zhejiang Chinese Medical University
Language: English
Subfield: Immunology and Allergy
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4416435858