P物质可提高气道过敏免疫疗法的疗效。

Substance P promotes immunotherapy efficacy for airway allergy.

作者信息

Wu Yongjin, Liu Yu, Wang Xinxin, Liu Huazhen, Wu Gaohui, Yang Liteng, Guan Li, Huang Qinmiao, Zeng Xianhai, Yang Pingchang

机构信息

Department of Allergy, Longgang ENT Hospital, Shenzhen Key Laboratory of ENT & Shenzhen ENT Institute, Shenzhen, China.

Departments of Respirology and Allergy, Third Affiliated Hospital, Shenzhen University, Shenzhen, China.

出版信息

World Allergy Organ J. 2022 Dec 15;16(1):100730. doi: 10.1016/j.waojou.2022.100730. eCollection 2023 Jan.

DOI:10.1016/j.waojou.2022.100730

PMID:36601262

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9791926/

Abstract

BACKGROUND

Allergen-specific immunotherapy (AIT) has been employed in the treatment of allergic diseases for many years. However, the effectiveness of AIT requires improvement. Substance P (SP) can interact with immune cells, modulate immune cell activity, and regulate immune reaction. The purpose of this study is to use SP as an immune regulator to enhance the therapeutic efficacy of AIT.

METHODS

An established mouse model of the airway allergy disorder (AAD) was employed with ovalbumin as a specific antigen. The AAD response was evaluated through established procedures. AAD mice were treated with AIT employing SP as an immune regulator. Dendritic cells were isolated from the airway tissues by magnetic cell sorting, and were analyzed by RNA sequencing (RNAseq).

RESULTS

We observed that after sensitization with ovalbumin, mice exhibited AAD-like symptoms, serum specific IgE, and Th2 polarization. The presence of SP in the course of sensitization prevented the development of AAD. Treating mice with SP by nasal instillations induced IL-10, but not TGF-β, in dendritic cells of the airway tissues. The most differentially expressed genes (DEG) in the dendritic cells were those related to the IL-10 expression, including , , and . The gene ontology analysis showed that these DEGs mainly mapped to the tachykinin-PI3K-AKT-mTOR pathway. The addition of SP substantially enhanced the therapeutic efficacy of AIT for AAD by inducing antigen specific type 1 regulatory T cells (Tr1 cells).

CONCLUSION

Acting as an immune regulator, SP promotes the therapeutic efficacy for AAD by inducing antigen specific Tr1 cells in the airway tissues.

摘要

背景

变应原特异性免疫疗法（AIT）已用于治疗过敏性疾病多年。然而，AIT的有效性仍有待提高。P物质（SP）可与免疫细胞相互作用，调节免疫细胞活性，并调控免疫反应。本研究旨在将SP用作免疫调节剂以提高AIT的治疗效果。

方法

采用已建立的以卵清蛋白为特异性抗原的气道过敏疾病（AAD）小鼠模型。通过既定程序评估AAD反应。将SP用作免疫调节剂，对AAD小鼠进行AIT治疗。通过磁珠细胞分选从气道组织中分离树突状细胞，并通过RNA测序（RNAseq）进行分析。

结果

我们观察到，用卵清蛋白致敏后，小鼠出现了类似AAD的症状、血清特异性IgE以及Th2极化。致敏过程中SP的存在可预防AAD的发展。通过滴鼻给小鼠施用SP可在气道组织的树突状细胞中诱导IL-10，但不诱导TGF-β。树突状细胞中差异表达最显著的基因（DEG）是那些与IL-10表达相关的基因，包括、和。基因本体分析表明，这些DEG主要映射到速激肽-PI3K-AKT-mTOR途径。添加SP可通过诱导抗原特异性1型调节性T细胞（Tr1细胞），显著提高AIT对AAD的治疗效果。