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

Abstract

Allergic rhinitis (AR) is a prevalent immune disorder driven by Th2-polarised inflammation, with current therapies primarily providing symptomatic relief rather than addressing the underlying immune dysfunction. Allergen-specific immunotherapy (AIT) holds promise for inducing long-term tolerance but is limited by poor mucosal delivery, enzymatic degradation of antigens, and inconsistent efficacy. A liposomal formulation co-encapsulating SpaCBA (probiotic protein) and ovalbumin (OVA) was engineered. Characterisation included in&#xa0;vitro/in vivo evaluations of immune modulation and therapeutic efficacy in a murine AR model. The SpaCBA-OVA liposome exhibited stable characteristics (size: 100&#x2009;&#xb1;&#x2009;25&#x2009;nm; zeta potential: -22&#x2009;&#xb1;&#x2009;3&#x2009;mV; 85% entrapment efficiency) and enhanced proteolytic resistance (>&#x2009;70% protein integrity after 48-h trypsin exposure vs. >&#x2009;90% degradation of free proteins). Bone marrow-derived DCs (BMDCs) internalised the liposome 3-3.5&#xd7; more efficiently via CD206/TLR2, adopting a semi-mature (CD86low/MHC-II) phenotype and secreting IL-10 (320&#x2009;&#xb1;&#x2009;30&#x2009;pg/mL) and TGF-&#x3b2; (280&#x2009;&#xb1;&#x2009;25&#x2009;pg/mL). RNA-seq identified 980 differentially expressed genes in T cells, with upregulation of Treg markers (FOXP3, IL-10) and downregulation of Th2 factors (GATA3, IL4). Epigenetic analysis confirmed 55% demethylation of the FOXP3 promoter. In AR mice, the liposome reduced sneezing and nasal rubbing by 60%-65% (p&#x2009;<&#x2009;0.001), decreased nasal eosinophils by 55%, normalised ZO-1/occludin expression (90% of controls), and reduced epithelial permeability (FITC-dextran flux). The SpaCBA-OVA liposome enhances mucosal delivery and stability of antigens, reprograms DCs to induce Treg-mediated tolerance via metabolic and epigenetic mechanisms, and effectively ameliorates AR pathology in mice. This formulation represents a promising targeted therapy for AR, addressing key limitations of current AIT.