MAF bZIP转录因子B（MAFB）通过恢复辅助性T细胞（Th）1/Th2/Th17失衡和上皮屏障功能障碍来减轻炎症，从而预防卵清蛋白诱导的过敏性鼻炎。
MAF bZIP Transcription Factor B (MAFB) Protected Against Ovalbumin-Induced Allergic Rhinitis via the Alleviation of Inflammation by Restoring the T Helper (Th) 1/Th2/Th17 Imbalance and Epithelial Barrier Dysfunction.
作者信息
Sun Yang, Liu Tiancong, Bai Weiliang
机构信息
Department of Otolaryngology Head and Neck Surgery, Shengjing Hospital of China Medical University, Shenyang, 110004, People's Republic of China.
出版信息
J Asthma Allergy. 2022 Feb 25;15:267-280. doi: 10.2147/JAA.S335560. eCollection 2022.
PURPOSE
This work aimed to investigate the effects of MAF bZIP transcription factor B (MAFB) on the progression of allergic rhinitis (AR).
PATIENTS AND METHODS
Nasal mucosa was isolated from AR patients and healthy individuals from Shengjing Hospital of China Medical University. The experimental procedures were approved by the Medical Ethics Committee of Shengjing Hospital of China Medical University (2019PS341K) in accordance with the Declaration of Helsinki. Informed consents were signed by participants or a parent/legal guardian of the participants under 18 years old of age. Then, an AR mouse model with MAFB overexpression was established with 25 μg ovalbumin (OVA) sensitization on day 0, 7, 14, followed by an injection with 1×10 TU/mL lentivirus MAFB on day 19 and a nasal challenge with 500 μg OVA from day 21 to 27.
RESULTS
The results revealed that MAFB was down-regulated in the nasal mucosa of AR patients. The up-regulation of MAFB protected the AR mice against the OVA-induced allergic symptoms (sneezing and nasal rubbing) by alleviating the OVA-induced epithelial thicknesses, goblet cell hyperplasia, and inflammation including the eosinophil and mast cell infiltration. Moreover, MAFB facilitated the T helper (Th) 1 response and inhibited the Th2 and Th17 responses by the down-regulation of T-box transcription factor 21 and the up-regulation of GATA binding protein-3 as well as retinoid-related orphan receptor-γt in the splenocytes of AR mice. MAFB was found to repress the differentiation of naive CD4 T cells into Th2 cells. Subsequently, MAFB overexpression reversed the OVA-induced enhancement of epithelial permeability, downregulation of tight junctions, and upregulation of cadherin-26, indicating the protective role of MAFB on epithelial barrier integrity.
CONCLUSION
MAFB protected against OVA-induced AR via the alleviation of inflammation by restoring the Th1/Th2/Th17 imbalance and epithelial barrier dysfunction.
目的
本研究旨在探讨MAF bZIP转录因子B（MAFB）对变应性鼻炎（AR）进展的影响。
患者与方法
从中国医科大学盛京医院的AR患者和健康个体中分离鼻黏膜。实验程序经中国医科大学盛京医院医学伦理委员会（2019PS341K）按照赫尔辛基宣言批准。参与者或18岁以下参与者的父母/法定监护人签署了知情同意书。然后，建立MAFB过表达的AR小鼠模型，于第0、7、14天用25μg卵清蛋白（OVA）致敏，第19天注射1×10 TU/mL慢病毒MAFB，第21至27天用500μg OVA进行鼻腔激发。
结果
结果显示，AR患者鼻黏膜中MAFB表达下调。MAFB的上调通过减轻OVA诱导的上皮厚度、杯状细胞增生以及包括嗜酸性粒细胞和肥大细胞浸润在内的炎症，保护AR小鼠免受OVA诱导的过敏症状（打喷嚏和鼻摩擦）。此外，MAFB通过下调AR小鼠脾细胞中T-box转录因子21以及上调GATA结合蛋白-3和视黄酸相关孤儿受体-γt，促进辅助性T（Th）1反应并抑制Th2和Th17反应。发现MAFB可抑制初始CD4 T细胞向Th2细胞的分化。随后，MAFB过表达逆转了OVA诱导的上皮通透性增强、紧密连接下调和钙黏蛋白-26上调，表明MAFB对上皮屏障完整性具有保护作用。
结论
MAFB通过恢复Th1/Th2/Th17失衡和上皮屏障功能障碍来减轻炎症，从而预防OVA诱导的AR。
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