关键词: AIt, allergen-specific immunotherapy Airway allergy disorder DEG, Differentially expressed gene Dendritic cells Immunotherapy Interleukin-10 SP, Substance P Semaphorin Tr1 cell, Type 1 regulatory T cell

来  源:   DOI:10.1016/j.waojou.2022.100730   PDF(Pubmed)

Abstract:
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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 Il10, Tac1r, and Mtor. 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).
UNASSIGNED: Acting as an immune regulator, SP promotes the therapeutic efficacy for AAD by inducing antigen specific Tr1 cells in the airway tissues.
摘要:
未经证实:变应原特异性免疫疗法(AIT)多年来一直用于变应性疾病的治疗。然而,AIT的有效性需要改进。P物质(SP)可以与免疫细胞相互作用,调节免疫细胞活性,调节免疫反应。这项研究的目的是使用SP作为免疫调节剂来增强AIT的治疗功效。
UNASSIGNED:采用建立的气道变态反应障碍(AAD)小鼠模型,卵清蛋白作为特异性抗原。通过建立的程序评估AAD反应。AAD小鼠用采用SP作为免疫调节剂的AIT处理。通过磁性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。
UNASSIGNED:我们观察到用卵清蛋白致敏后,小鼠表现出AAD样症状,血清特异性IgE,和Th2极化。在致敏过程中SP的存在阻止了AAD的发展。通过鼻滴注用SP治疗小鼠诱导IL-10,而不是TGF-β,在气道组织的树突状细胞中。树突状细胞中差异表达最多的基因(DEG)是与IL-10表达相关的基因,包括Il10Tac1r,还有Mtor.基因本体论分析表明,这些DEGs主要定位在速激肽-PI3K-AKT-mTOR通路。SP的添加通过诱导抗原特异性1型调节性T细胞(Trl细胞)显著增强AIT对AAD的治疗功效。
未经批准:充当免疫调节剂,SP通过在气道组织中诱导抗原特异性Trl细胞来促进AAD的治疗功效。
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