Department of Otolaryngology Head and Neck Surgery, Jiangxi Medical College, Nanchang University, No. 1, Minde Road, Nanchang, 330006, Jiangxi Province, China.
J Nanobiotechnology. 2024 Sep 19;22(1):575. doi: 10.1186/s12951-024-02748-2.
Allergic rhinitis (AR) is a condition with limited treatment options. This study investigates the potential use of mesenchymal stem cell (MSC) nanovesicles as a novel therapy for AR. Specifically, the study explores the underlying mechanisms of MSC nanovesicle therapy by targeting dendritic cells (DCs). The researchers fabricated DC-targeted P-D2-EVs nanovesicles and characterized their properties. Transcriptomic sequencing and single-cell sequencing analyses were performed to study the impact of P-D2-EVs on AR mice, identifying core genes involved in the treatment. In vitro cell experiments were conducted to validate the effects of P-D2-EVs on DC metabolism, Th2 differentiation, and ILC2 activation. The results showed that P-D2-EVs efficiently targeted DCs. Transcriptomic sequencing analysis revealed differential expression of 948 genes in nasal tissue DCs of mice treated with P-D2-EVs. Single-cell sequencing further revealed that P-D2-EVs had inhibitory effects on DC activation, Th2 differentiation, and ILC2 activation, with Fut1 identified as the core gene. Validation experiments demonstrated that P-D2-EVs improved IL10 metabolism in DCs by downregulating Fut1 expression, thereby suppressing Th2 differentiation and ILC2 activation. Animal experiments confirmed the inhibitory effects of P-D2-EVs and their ability to ameliorate AR symptoms in mice. The study suggests that P-D2-EVs reshape DC metabolism and suppress Th2 differentiation and ILC2 activation through the inhibition of the Fut1/ICAM1/P38 MAPK signaling pathway, providing a potential therapeutic approach for AR.
变应性鼻炎(AR)的治疗选择有限。本研究探讨了间充质干细胞(MSC)纳米囊泡作为治疗 AR 的一种新疗法的潜力。具体而言,该研究通过靶向树突状细胞(DC)来探索 MSC 纳米囊泡治疗的潜在机制。研究人员制备了靶向 DC 的 P-D2-EVs 纳米囊泡,并对其特性进行了表征。进行了转录组测序和单细胞测序分析,以研究 P-D2-EVs 对 AR 小鼠的影响,确定参与治疗的核心基因。进行了体外细胞实验,以验证 P-D2-EVs 对 DC 代谢、Th2 分化和 ILC2 激活的影响。结果表明,P-D2-EVs 能够有效地靶向 DC。转录组测序分析显示,用 P-D2-EVs 处理的小鼠鼻组织 DC 中 948 个基因的表达存在差异。单细胞测序进一步显示,P-D2-EVs 对 DC 激活、Th2 分化和 ILC2 激活具有抑制作用,其中 Fut1 被鉴定为核心基因。验证实验表明,P-D2-EVs 通过下调 Fut1 表达改善了 DC 中 IL10 的代谢,从而抑制了 Th2 分化和 ILC2 激活。动物实验证实了 P-D2-EVs 的抑制作用及其在改善 AR 症状方面的能力。该研究表明,P-D2-EVs 通过抑制 Fut1/ICAM1/P38 MAPK 信号通路重塑 DC 代谢并抑制 Th2 分化和 ILC2 激活,为 AR 提供了一种潜在的治疗方法。