Intranasal administration of regulatory dendritic cells is useful for the induction of nasal mucosal tolerance in a mice model of allergic rhinitis

Abstract

Background Intranasally administered dendritic cells (DCs) migrate into blood and thymus to induce immune responses. Regulatory dendritic cells (DCs) are also useful agents for allergy control. However, to the best of our knowledge, the effects of intranasal administration of regulatory DCs on allergy have not been reported until now. Therefore, we examined the effects of intranasal route of administration of CD40-silenced DCs on allergic responses and compared these with the effects of other administration routes, based on our previous findings on the inhibitory effects of CD40-silenced DCs on allergic responses. Methods Mice with allergic rhinitis were treated intranasally, subcutaneously, intraperitoneally, or intravenously with CD40-silenced ovalbumin (OVA)-pulsed DCs that were transfected with CD40 siRNAs and pulsed with OVA antigen. The effects of these DCs on allergic reactions and symptoms were estimated. Results Intranasal, subcutaneous, intraperitoneal, or intravenous administration of OVA-pulsed CD40-silenced DCs inhibited allergic responses and symptoms in mice. Furthermore, intranasal administration of OVA-pulsed CD40-silenced DCs significantly reduced allergic symptoms and the number of eosinophils in the nasal mucosa compared with subcutaneous, intraperitoneal, or intravenous administration of these DCs. Intranasal administration of OVA-pulsed CD40-silenced DCs resulted in significantly up-regulated IL-10, IL-35, and Foxp3 expression, and enhanced the percentage of CD11c + CD40 − and CD4 + CD25 + cells within the cervical lymph nodes compared to subcutaneous, intraperitoneal, or intravenous routes of administration. Conclusions We believe that this is the first report to demonstrate that regulatory DCs infiltrate into the cervical lymph nodes after intranasal administration of these cells and that intranasal administration of regulatory DCs is more effective for the induction of tolerance in the nasal mucosa than subcutaneous, intraperitoneal, or intravenous administration.

Schistosoma japonicum-derived peptide SJMHE1 ameliorates allergic symptoms and responses in mice with allergic rhinitis

“…OVA intraperitoneal injection followed by repeated upper-airway OVA challenge (intranasal) was used to induce allergic inflammation of the nasal mucosa, which is the well-established protocols of AR model ( Suzuki et al., 2020 ; Fang et al., 2021 ). The nasal symptoms (eg, rubbing and sneezing) and antigen-specific IgE in serum play important roles in AR diagnosis ( Greiner et al., 2011 ).…”

“…Six week female BALB/c mice were purchased from the Comparative Medicine Centre of Yangzhou University (Yangzhou, China). Experimental AR was induced according to a previous report ( Suzuki et al., 2020 ). Briefly, mice were sensitized with OVA (10 μg) and 2 mg of Al(OH) 3 in 200 μl PBS intraperitoneally on days 0, 7 and 14.…”

Mesenchymal Stem Cell-derived Exosome: An Interesting Nanocarrier to Improve Allergen-specific Intranasal Immunotherapy

“…In this case, encapsulation of the allergen in nano-sized vesicles/particles to increase the delivery efficiency could reduce the risk of side effects by stabilizing and increasing its immunogenicity even at lower doses. 9,10 Exosomes (Exo) are biological nanoparticles capable of delivering cargoes such as small RNAs and proteins. Various cells release these vesicles in the endosomal network and play important roles in intercellular interactions while possessing beneficial properties, such as biocompatibility, low clearance, low long-term accumulation, loss of toxicity, and accelerated cellular uptake.…”