Sublingual immunotherapy suppresses Th2-type immune response in the allergic rhinitis mouse model by inhibiting the activation of the NFκB pathway

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. 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. 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. 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. Allergic rhinitis (AR), commonly known as hay fever, affects millions worldwide, causing uncomfortable symptoms like sneezing, runny nose, and itchy eyes when the body overreacts to harmless substances like pollen or dust. This study investigated how sublingual immunotherapy (SLIT) works to reduce these symptoms. SLIT is a treatment where small, gradually increasing amounts of the allergen are placed under the tongue to help the body become less sensitive to it over time.Researchers found that SLIT works by calming an overactive immune response. Specifically, it reduces activity in a key immune pathway called NFκB, which drives allergic reactions. When they used a drug to block NFκB, SLIT worked even better. When they prevented NFκB from functioning normally, SLIT’s benefits were reduced. This research explains why SLIT is effective for treating allergies. Understanding this mechanism could lead to improved treatments that provide better symptom relief for people with allergic rhinitis. For now, it supports SLIT as a valuable long-term treatment option that can provide lasting relief from allergy symptoms.