Intranasal administration of regulatory dendritic cells is useful for the induction of nasal mucosal tolerance in a mice model of allergic rhinitis.
Intranasal administration of regulatory dendritic cells is useful for the induction of nasal mucosal tolerance in a mice model of allergic rhinitis.
复制标题
鼻内施用调节性树突细胞可用于诱导过敏性鼻炎小鼠模型的鼻粘膜耐受性。
DOI：
10.1016/j.waojou.2020.100447
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Nakamura Y.
中科院分区：
文献类型：
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作者：
Suzuki M;Yokota M;Kanemitsu Y;Min WP;Ozaki S;Nakamura Y.
研究背景鼻内注射树突状细胞（dendritic cells，DC）可迁移至血液和胸腺，诱导机体产生免疫应答.调节性树突细胞（DC）也是用于过敏控制的有用试剂。然而，据我们所知，鼻内给药调节性DC对变态反应的影响至今未见报道。因此，基于我们先前关于CD 40沉默的DC对过敏反应的抑制作用的发现，我们检查了鼻内途径施用CD 40沉默的DC对过敏反应的作用，并将这些与其他施用途径的作用进行比较。或静脉内注射用CD 40沉默的卵清蛋白（OVA）脉冲的DC，所述DC用CD 40 siRNA转染并用OVA抗原脉冲。这些DC对过敏反应和症状的影响进行了estimated.ResultsIntranasal，皮下，腹腔内，或静脉内给药的OVA脉冲CD 40沉默的DC抑制小鼠的过敏反应和症状。此外，与皮下、腹膜内或静脉内给予这些DC相比，鼻内给予OVA脉冲的CD 40沉默DC显著减少过敏症状和鼻粘膜中嗜酸性粒细胞的数量。与皮下、腹膜内、皮下和腹膜内相比，鼻腔内给予OVA脉冲的CD 40沉默的DC导致IL-10、IL-35和Foxp 3表达显著上调，并增加了颈部淋巴结内CD 11 c + CD 40 −和CD 4 + CD 25+细胞的百分比。结论：我们认为这是第一个证明调节性DC浸润到颈部淋巴结的报道并且鼻内施用调节性DC比皮下、腹膜内或静脉内施用更有效地诱导鼻粘膜中的耐受。
BackgroundIntranasally 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.MethodsMice 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.ResultsIntranasal, 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, andFoxp3expression, 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.ConclusionsWe 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.