Arginine-Rich Cell-Penetrating Peptide-Mediated Transduction of Mouse Nasal Cells with FOXP3 Protein Alleviates Allergic Rhinitis.
Toru MiwaYumi TakemiyaKazuki AmesaraHiroko KawaiYuichi TeranishiPublished in: Pharmaceutics (2023)
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.
Keyphrases
- regulatory t cells
- chronic rhinosinusitis
- allergic rhinitis
- single cell
- mouse model
- drug delivery
- transcription factor
- cell therapy
- dendritic cells
- induced apoptosis
- amino acid
- binding protein
- flow cytometry
- nitric oxide
- protein protein
- gene expression
- cell cycle arrest
- immune response
- drug induced
- risk assessment
- oxidative stress
- small molecule
- signaling pathway
- case report
- high speed