4.7 Article

Arginine-Rich Cell-Penetrating Peptide-Mediated Transduction of Mouse Nasal Cells with FOXP3 Protein Alleviates Allergic Rhinitis

Journal

PHARMACEUTICS
Volume 15, Issue 6, Pages -

Publisher

MDPI
DOI: 10.3390/pharmaceutics15061770

Keywords

allergic rhinitis; cell-penetrating peptide; FOXP3; ovalbumin-specific IgE transgenic mice

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This study explores the potential of using polyarginine-fused FOXP3 protein as a novel therapeutic strategy for allergic rhinitis. The results show that this approach can induce Treg-like cell generation in the nasal epithelium and enhance allergen tolerance. Polyarginine-mediated FOXP3 protein transduction could potentially offer an alternative to conventional intranasal drug application for nasal drug delivery.
Intranasal corticosteroids are effective medications against allergic rhinitis (AR). However, mucociliary clearance promptly eliminates these drugs from the nasal cavity and delays their onset of action. Therefore, a faster, longer-lasting therapeutic effect on the nasal mucosa is required to enhance the efficacy of AR management. Our previous study showed that polyarginine, a cell-penetrating peptide, can deliver cargo to nasal cells; moreover, polyarginine-mediated cell-nonspecific protein transduction into the nasal epithelium exhibited high transfection efficiency with minimal cytotoxicity. In this study, poly-arginine-fused forkhead box P3 (FOXP3) protein, the master transcriptional regulator of regulatory T cells (Tregs), was administered into the bilateral nasal cavities of the ovalbumin (OVA)-immunoglobulin E mouse model of AR. The effects of these proteins on AR following OVA administration were investigated using histopathological, nasal symptom, flow cytometry, and cytokine dot blot analyses. Polyarginine-mediated FOXP3 protein transduction induced Treg-like cell generation in the nasal epithelium and allergen tolerance. Overall, this study proposes FOXP3 activation-mediated Treg induction as a novel and potential therapeutic strategy for AR, providing a potential alternative to conventional intranasal drug application for nasal drug delivery.

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