de Aragão-França Luciana Souza, Aragão-França Luciana S, Rocha Viviane Costa Junqueira, Rocha Viviane C J, Cronemberger-Andrade Andre, da Costa Fábio Henrique Brasil, Costa F H B, Vasconcelos Juliana Fraga, Vasconcelos José Fernandes, Athanazio Daniel Abensur, Silva Daniela Nascimento, Santos Emanuelle Souza, Santos E S, Meira Cássio Santana, Araujo Cintia Figueiredo, Araújo C F, Cerqueira Jéssica Vieira, Cardillo Fabíola, Alcântara-Neves Neuza Maria, Soares Milena Botelho Pereira, Pontes de Carvalho Lain Carlos, Pontes-de-Carvalho Lain C
Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Bahia, Brazil.
Centro de Biotecnologia e Terapia Celular, Hospital São Rafael, Salvador, Bahia, Brazil.
Allergy Asthma Immunol Res. 2018 Jul;10(4):406-419. doi: 10.4168/aair.2018.10.4.406.
The use of tolerogenic dendritic cells (TolDCs) to control exacerbated immune responses may be a prophylactic and therapeutic option for application in autoimmune and allergic conditions. The objective of this work was to evaluate the effects of TolDC administration in a mouse model of allergic airway inflammation caused by mite extract.
Mouse bone marrow-derived TolDCs were induced by incubation with granulocyte-macrophage colony-stimulating factor (GM-CSF) and dexamethasone, and then characterized by flow cytometry and cytokine production by enzyme-linked immunosorbent assay (ELISA). For the in vivo model of Blomia tropicalis-induced allergy, mice transplanted with antigen-pulsed TolDCs were sensitized intraperitoneally with B. tropicalis mite extract (BtE) adsorbed to aluminium hydroxide. After challenge by nasal administration of BtE, bronchoalveolar lavage fluid (BALF), lungs, spleen and serum were collected for analysis.
Induction of TolDCs was efficiently achieved as shown by low expression of major histocompatibility complex (MHC) II, programmed death-ligand (PD-L) 2 and pro-inflammatory cytokine production, and up-regulation of interleukin (IL)-10, upon LPS stimulation in vitro. Transplantation of 1 or 2 doses of BtE-pulsed TolDCs reduced the number of inflammatory cells in BALF and lungs as well as mucus deposition. Moreover, compared to saline-injected controls, TolDC-treated mice showed lower serum levels of anti-BtE immunoglobulin E (IgE) antibodies as well as reduced Gata3 and IL-4 gene expression in the lungs and decreased IFN-γ levels in the supernatant of splenocyte cultures Transplantation of TolDCs increased the percentage of the regulatory T cells in the spleen and the lungs.
Preventive treatment with TolDCs protects against dust mite-induced allergy in a mouse model, reinforcing the use of tolerogenic dendritic cells for the management of allergic conditions.
使用耐受性树突状细胞（TolDCs）来控制过度的免疫反应，可能是一种用于自身免疫和过敏病症的预防和治疗选择。本研究的目的是评估在由螨提取物引起的过敏性气道炎症小鼠模型中给予TolDCs的效果。
通过与粒细胞巨噬细胞集落刺激因子（GM-CSF）和地塞米松孵育诱导小鼠骨髓来源的TolDCs，然后通过流式细胞术进行表征，并通过酶联免疫吸附测定（ELISA）检测细胞因子的产生。对于热带无爪螨诱导的过敏体内模型，用吸附于氢氧化铝的热带无爪螨螨提取物（BtE）对移植了抗原脉冲TolDCs的小鼠进行腹腔致敏。经鼻腔给予BtE激发后，收集支气管肺泡灌洗液（BALF）、肺、脾和血清进行分析。
如体外LPS刺激时主要组织相容性复合体（MHC）II、程序性死亡配体（PD-L）2低表达以及促炎细胞因子产生减少，白细胞介素（IL）-10上调所示，TolDCs的诱导有效实现。移植1或2剂BtE脉冲TolDCs可减少BALF和肺中的炎症细胞数量以及黏液沉积。此外，与注射生理盐水的对照组相比，经TolDC处理的小鼠血清中抗BtE免疫球蛋白E（IgE）抗体水平较低，肺中Gata3和IL-4基因表达降低，脾细胞培养上清液中IFN-γ水平降低。TolDCs移植增加了脾和肺中调节性T细胞的百分比。
在小鼠模型中，用TolDCs进行预防性治疗可预防尘螨诱导的过敏，这进一步证明了使用耐受性树突状细胞来管理过敏病症的可行性。
