SpaCBA-OVA Liposome Reprograms Immune Tolerance to Ameliorate Allergic Rhinitis via DC-T Cell Crosstalk.

Area of Science:

• Immunology
• Nanotechnology
• Drug Delivery

Background:

• Allergic rhinitis (AR) is a common immune disorder driven by Th2 inflammation, with current treatments offering only symptomatic relief.
• Allergen-specific immunotherapy (AIT) aims for long-term tolerance but faces challenges in mucosal delivery, antigen stability, and efficacy.

Purpose of the Study:

• To engineer and evaluate a liposomal formulation co-encapsulating a probiotic protein (SpaCBA) and ovalbumin (OVA) for improved AR treatment.
• To assess the immune modulation and therapeutic efficacy of the SpaCBA-OVA liposome in a murine model of AR.

Main Methods:

• Characterization of liposome stability, size, zeta potential, and entrapment efficiency.
• In vitro assessment of antigen stability against enzymatic degradation.
• In vivo studies in a murine AR model evaluating immune cell responses, gene expression, epigenetic modifications, and AR symptom amelioration.

Main Results:

• The SpaCBA-OVA liposome demonstrated excellent stability, enhanced proteolytic resistance, and efficient uptake by dendritic cells (DCs).
• Liposome treatment induced a semi-mature DC phenotype, promoting IL-10 and TGF-β secretion and reprogramming T cells towards a Treg profile with FOXP3 promoter demethylation.
• In AR mice, the liposome significantly reduced AR symptoms, nasal eosinophils, and epithelial permeability, while restoring barrier function.

Conclusions:

• The SpaCBA-OVA liposome effectively overcomes limitations of current AIT by enhancing mucosal delivery and stability of antigens.
• This formulation reprograms DCs to induce Treg-mediated tolerance through metabolic and epigenetic pathways, offering a promising targeted therapy for AR.