Li Yeshan, Yu Qijun, Zhao Wenxue, Zhang Jiaxiang, Liu Wentao, Huang Mao, Zeng Xiaoning
Department of Respiratory & Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, China.
Lung Biology Center, Department of Medicine, University of California San Francisco, San Francisco, California 94143, USA.
Mol Immunol. 2017 Nov;91:209-217. doi: 10.1016/j.molimm.2017.09.012. Epub 2017 Sep 30.
To date, although a promising anti-inflammatory activity of oligomeric proanthocyanidins (OPCs) has been observed in asthma, the mechanism responsible for these immunomodulatory properties remains obscure. Dendritic cells (DCs) that reside in the airway have been widely perceived as an important contributor to asthma. Our study was to demonstrate OPCs' effects on maturation and immunoregulation of pulmonary CD11c dendritic cells (DCs). BALB/c mice were exposed to ovalbumin (OVA) to induce murine model of asthma. In addition, pulmonary DCs and bone marrow-derived DCs (BMDCs) cultures were used to evaluate impacts of OPCs on DCs function. The results obtained here indicated that OPCs treatment dramatically reduced airway inflammation, such as the infiltration of inflammatory cells and the levels of allergen-specific serum IgE and Th2 cytokines. The expression of co-stimulatory molecules especially CD86 distributed on pulmonary DCs and bone marrow-derived DCs (BMDCs) also markedly declined. The phosphorylation of cAMP responsive element-binding protein (CREB) was significantly inhibited while no changes were observed in the expression of cAMP responsive element modulator (CREM). By transferring BMDCs into the airways of naïve mice, we found that OPCs-treated DCs (DC+OVA+OPC) were much less potent in promoting CD4 T cells proliferation than OVA-pulsed DCs (DC+OVA), followed by the ameliorated eosinophilic inflammation in airway. Our findings tailor a novel profile of OPCs in the regulation of DCs function, shedding new light on the therapeutic potential of OPCs in asthma management.
迄今为止,尽管已观察到低聚原花青素(OPCs)在哮喘中具有有前景的抗炎活性,但其免疫调节特性的机制仍不清楚。驻留在气道中的树突状细胞(DCs)被广泛认为是哮喘的重要促成因素。我们的研究旨在证明OPCs对肺部CD11c树突状细胞(DCs)成熟和免疫调节的影响。将BALB/c小鼠暴露于卵清蛋白(OVA)以诱导哮喘小鼠模型。此外,使用肺DCs和骨髓来源的DCs(BMDCs)培养物来评估OPCs对DCs功能的影响。此处获得的结果表明,OPCs治疗显著减轻了气道炎症,如炎症细胞浸润以及过敏原特异性血清IgE和Th2细胞因子水平。分布在肺DCs和骨髓来源的DCs(BMDCs)上的共刺激分子尤其是CD86的表达也明显下降。cAMP反应元件结合蛋白(CREB)的磷酸化受到显著抑制,而cAMP反应元件调节剂(CREM)的表达未观察到变化。通过将BMDCs转移到未致敏小鼠的气道中,我们发现经OPCs处理的DCs(DC + OVA + OPC)在促进CD4 T细胞增殖方面的能力远低于OVA脉冲DCs(DC + OVA),随后气道中的嗜酸性炎症得到改善。我们的研究结果揭示了OPCs在调节DCs功能方面的新特性,为OPCs在哮喘管理中的治疗潜力提供了新的线索。