Department of Otolaryngology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
Department of Otolaryngology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
Int Immunopharmacol. 2019 May;70:216-224. doi: 10.1016/j.intimp.2019.02.045. Epub 2019 Mar 6.
House dust mites, including Der p1, are common allergens. The current study was designed to explore the allergen-specific immune tolerance effects of Der p1-modified dendritic cells (DCs) through IL-4, IL-10 and IL-13 on an allergic rhinitis (AR) mouse model.
A lentivirus was modified to express Derp1. Then, immature DCs from mice were infected with this modified lentivirus to generate a lenti-Derp1-GFP DCs. 24 mice were random divided into four groups (n = 6 each), AR mouse were sensitized by Derp1 allergens and treated with lenti-GFP DCs (GFP-DC/AR group), or lenti-Derp1-GFP DCs (Der p1-DC/AR group) and dexamethasone (Dex/AR group), mice in the control group were treated with PBS instead of Der p1 then also intraperitoneally injected with 5 × 10 lenti-GFP DCs/mouse. AR symptoms expressed by each mouse were recorded. The proportions of CD4CD25Foxp3 regulatory T cells among CD4 T cells in the peripheral blood, and mRNA and protein expression levels of IL-4, IL-10, and IL-13 were measured.
DCs infected with lenti-Derp1-GFP stimulated the maturation of DCs. Compared with the GFP-DC/AR group, mice in the Der p1-DC/AR group showed an ameliorated allergic response, a significant decrease in the levels of serum IgE, IgG1, and histamine, and a decrease in the expression of IL-4 and IL-13 mRNA and protein in the nasal mucosa. The expression of IL-10 increased in the Der p1-DC/AR group to a level similar to that observed in the Dex/AR group.
These results indicate that Der p1-modified DCs have therapeutic potential for AR via downregulation of IL-4 and IL-13, and upregulation of IL-10.
屋尘螨包括 Der p1 在内，是常见的过敏原。本研究旨在通过白细胞介素 4（IL-4）、白细胞介素 10（IL-10）和白细胞介素 13（IL-13），探讨 Der p1 修饰的树突状细胞（DC）对变应性鼻炎（AR）小鼠模型的过敏原特异性免疫耐受作用。
构建携带 Derp1 的慢病毒，然后用该修饰慢病毒感染小鼠未成熟的 DC，生成 lenti-Derp1-GFP DC。将 24 只小鼠随机分为 4 组（每组 6 只），AR 小鼠用 Derp1 过敏原致敏，用 lenti-GFP DC（GFP-DC/AR 组）或 lenti-Derp1-GFP DC（Der p1-DC/AR 组）和地塞米松（Dex/AR 组）治疗，对照组小鼠用 PBS 代替 Der p1 处理，然后每只小鼠腹腔注射 5×10 lenti-GFP DC。记录每只小鼠的 AR 症状，检测外周血 CD4CD25Foxp3 调节性 T 细胞（Treg）在 CD4 T 细胞中的比例，以及 IL-4、IL-10 和 IL-13 的 mRNA 和蛋白表达水平。
感染 lenti-Derp1-GFP 的 DC 刺激 DC 成熟。与 GFP-DC/AR 组相比，Der p1-DC/AR 组的过敏反应得到改善，血清 IgE、IgG1 和组胺水平显著降低，鼻黏膜中 IL-4 和 IL-13 mRNA 和蛋白表达降低，IL-10 表达增加，与 Dex/AR 组相似。
这些结果表明，Der p1 修饰的 DC 通过下调 IL-4 和 IL-13，上调 IL-10，对 AR 具有治疗潜力。
