Co-delivery of allergen epitope fragments and R848 inhibits food allergy by inducing tolerogenic dendritic cells and regulatory T cells

Abstract

Jingyi Hong,1–3,* Xiaojun Xiao,2,3,* Qichan Gao,2,* Shanshan Li,2 Bei Jiang,2 Xizhuo Sun,1 Pixin Ran,3 Pingchang Yang21Department of Allergy, The Third Affiliated Hospital of Shenzhen University, Shenzhen 518020, People’s Republic of China; 2Research Center of Allergy & Immunology, Department of Medicine, Shenzhen University, Shenzhen 518055, People’s Republic of China; 3State Key Laboratory of Respiratory Disease, Department of Allergy and Clinical Immunology, Guangzhou Medical University, Guangzhou 510006, People’s Republic of ChinaCorrespondence: Pixin RanState Key Laboratory of Respiratory Disease, Department of Allergy and Clinical Immunology, Guangzhou Medical University, Jingxiu Road, Xinzao, Panyu District, Shenzhen 510006, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected] YangResearch Center of Allergy & Immunology,Department of Medicine, Shenzhen University, Room A7-509 at Xili Campus, 1066 Xueyuan Blvd, Shenzhen 518055, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected]*These authors contributed equally to this workBackground: Food allergy (FA) is a significant public health problem. The therapeutic efficacy for FA is unsatisfactory currently. The breakdown of intestinal immune tolerance is associated with the pathogenesis of FA. Therefore, it is of great significance to develop novel therapeutic methods to restore immune tolerance in treating FA.Methods: We proposed an oral administration strategy to treat FA by co-delivering food allergen epitope fragment (peptide: IK) and adjuvant R848 (TLR7 ligand) in the mPEG–PDLLA nanoparticles (PPLA-IK/R848 NPs). The generation of tolerogenic dendritic cells (DCs) and regulatory T cells (Tregs) induced by PPLA-IK/R848 NPs were evaluated in vitro and in vivo. The therapeutic effects of PPLA-IK/R848 NPs were also assessed in an OVA-induced FA model.Results: PPLA-IK/R848 NPs could efficiently deliver IK to DCs to drive DCs into the tolerogenic phenotypes and promote the differentiation of Tregs in vitro and in vivo, significantly inhibited FA responses through the recovery of intestinal immune tolerance.Conclusion: Oral administration of PPLA-IK/R848 NPs could efficiently deliver IK and R848 to intestinal DCs and stimulate DCs into allergen tolerogenic phenotype. These tolerogenic DCs could promote the differentiation of Tregs, which significantly protected mice from food allergic responses. This study provided an efficient formulation to alleviate FA through the recovery of immune tolerance.Keywords: food allergy, co-delivery, allergen epitope fragment, R848, dendritic cells, Tregs

Keywords

• Food allergy
• co-delivery
• allergen epitope fragment
• R848
• dendritic cells
• Tregs