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Allergen\u2010specific immunotherapy (AIT) holds promise for inducing long\u2010term tolerance but is limited by poor mucosal delivery, enzymatic degradation of antigens, and inconsistent efficacy. A liposomal formulation co\u2010encapsulating SpaCBA (probiotic protein) and ovalbumin (OVA) was engineered. Characterisation included in\u00a0vitro\/in vivo evaluations of immune modulation and therapeutic efficacy in a murine AR model. The SpaCBA\u2010OVA liposome exhibited stable characteristics (size: 100\u2009\u00b1\u200925\u2009nm; zeta potential: \u221222\u2009\u00b1\u20093\u2009mV; 85% entrapment efficiency) and enhanced proteolytic resistance (&gt;\u200970% protein integrity after 48\u2010h trypsin exposure vs. &gt;\u200990% degradation of free proteins). Bone marrow\u2010derived DCs (BMDCs) internalised the liposome 3\u20133.5\u00d7 more efficiently via CD206\/TLR2, adopting a semi\u2010mature (CD86low\/MHC\u2010II\n                    <jats:sup>high<\/jats:sup>\n                    ) phenotype and secreting IL\u201010 (320\u2009\u00b1\u200930\u2009pg\/mL) and TGF\u2010\u03b2 (280\u2009\u00b1\u200925\u2009pg\/mL). RNA\u2010seq identified 980 differentially expressed genes in T cells, with upregulation of Treg markers (FOXP3, IL\u201010) 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%\u201365% (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001), decreased nasal eosinophils by 55%, normalised ZO\u20101\/occludin expression (90% of controls), and reduced epithelial permeability (FITC\u2010dextran flux). The SpaCBA\u2010OVA liposome enhances mucosal delivery and stability of antigens, reprograms DCs to induce Treg\u2010mediated 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.\n                  <\/jats:p>","DOI":"10.1111\/imm.70078","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T07:41:21Z","timestamp":1764920481000},"page":"725-735","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>SpaCBA<\/scp>\n                    \u2010\n                    <scp>OVA<\/scp>\n                    Liposome Reprograms Immune Tolerance to Ameliorate Allergic Rhinitis via\n                    <scp>DC<\/scp>\n                    \u2010T Cell Crosstalk"],"prefix":"10.1111","volume":"177","author":[{"given":"Jinna","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Pediatric Otolaryngology, Shenzhen Hospital Southern Medical University  Shenzhen China"},{"name":"Shenzhen School of Clinical Medicine Southern Medical University  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinmei","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head &amp; Neck Surgery Second Hospital of Shanxi Medical University  Taiyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihua","family":"Mo","sequence":"additional","affiliation":[{"name":"Department of Pediatric Otolaryngology, Shenzhen Hospital Southern Medical University  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aizhi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine Second Hospital of Shanxi Medical University  Taiyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinbiao","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Pediatric Otolaryngology, Shenzhen Hospital Southern Medical University  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialiang","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Pediatric Otolaryngology, Shenzhen Hospital Southern Medical University  Shenzhen China"},{"name":"State Key Laboratory of Respiratory Diseases Allergy Division at Shenzhen University and Institute of Allergy &amp; 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Immunology, Shenzhen Key Laboratory of Allergy &amp; Immunology Shenzhen University School of Medicine  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dabo","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Otolaryngology, Shenzhen Hospital Southern Medical University  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangqian","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Pediatric Otolaryngology, Shenzhen Hospital Southern Medical University  Shenzhen China"},{"name":"Shenzhen School of Clinical Medicine Southern Medical University  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,4]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.12968\/hmed.2021.0570"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pop.2023.01.003"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.15044"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2018.03.028"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-020-00227-0"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.iac.2015.12.004"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/0194599814561600"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.iac.2020.06.001"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alit.2020.08.002"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.983621"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11175154"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.03949-14"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07251-0"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines11030495"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1777"},{"key":"e_1_2_11_17_1","first-page":"20119","article-title":"Autoantigenic Peptide and Immunomodulator Codelivery System for Rheumatoid Arthritis Treatment by Reestablishing Immune Tolerance","volume":"16","author":"Mai Y.","year":"2024","journal-title":"ACS Applied Materials & Interfaces"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2022.121571"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.b21-00924"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.10295"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature23475"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.928621"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.07.015"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2006.02321.x"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alit.2017.12.001"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/clt2.12029"}],"container-title":["Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imm.70078","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/imm.70078","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imm.70078","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T09:30:42Z","timestamp":1772962242000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/imm.70078"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,4]]},"references-count":25,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1111\/imm.70078"],"URL":"https:\/\/doi.org\/10.1111\/imm.70078","archive":["Portico"],"relation":{},"ISSN":["0019-2805","1365-2567"],"issn-type":[{"value":"0019-2805","type":"print"},{"value":"1365-2567","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,4]]},"assertion":[{"value":"2025-09-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}