Respiratory Division of Zhongshan Hospital, Shanghai Institute of Respiratory Disease, Fudan University, Shanghai, China.
Respiratory Division of the Affiliated Hospital of Qingdao University, Qingdao, China.
J Cell Physiol. 2019 May;234(5):6642-6653. doi: 10.1002/jcp.27422. Epub 2018 Oct 26.
Interleukin-27 (IL-27) modulates CD4+ T-cell differentiation and function. The aim of this study is to investigate the effect and molecular mechanisms of IL-27 on the development of asthma.
IL-27 was intranasally administered in an ovalbumin-induced asthma model, and lung mononuclear cells and different Th cell classes were detected by fluorescence-activated cell sorting. The effect and mechanisms of IL-27 on human bronchial epithelial (HBE) cells were investigated by measuring changes in chemotactic factors, cytokines, transcription factors, and signaling pathways.
We found that intranasal administration of IL-27 could attenuate airway inflammation and hyperresponsiveness, upregulate the type 1 T helper (Th1)-T memory (Tm) cells and regulatory T (Treg) cells subgroups of lung tissue lymphocytes, and diminish the levels of type 2 T helper (Th2) cytokines. IL-27 upregulated the expression of C-C motif chemokine ligand 2 (CCL2), CCL3, and CCL4 in HBE cells and promoted the production of chemotactic factors to attract monocyte recruitment. Recruited monocytes secondarily secreted IL-27 to influence HBE cells in a positive feedback cycle. After IL-27 intervention, signal transducer and activator of transcription 1 (STAT1) phosphorylation increased, while STAT4 and STAT6 phosphorylation declined.
Preventative intranasal administration of IL-27 can recruit more IL-27-secreted monocytes to the airway and change the different T-cell classes in lung. The improved Th1 environment helps to alleviate Th2-mediated allergic asthma by repairing the STAT1 pathway but not the STAT4 pathway.
白细胞介素-27（IL-27）调节 CD4+T 细胞的分化和功能。本研究旨在探讨 IL-27 对哮喘发生发展的影响及其分子机制。
在卵清蛋白诱导的哮喘模型中经鼻给予 IL-27，通过流式细胞术检测肺单核细胞和不同的 Th 细胞亚群。通过测量趋化因子、细胞因子、转录因子和信号通路的变化，研究 IL-27 对人支气管上皮（HBE）细胞的作用及机制。
我们发现经鼻给予 IL-27 可减轻气道炎症和高反应性，上调肺组织淋巴细胞中 1 型 T 辅助（Th1）-T 记忆（Tm）细胞和调节性 T（Treg）细胞亚群，并降低 2 型 T 辅助（Th2）细胞因子的水平。IL-27 上调 HBE 细胞中 C-C 基序趋化因子配体 2（CCL2）、CCL3 和 CCL4 的表达，并促进趋化因子的产生，以吸引单核细胞募集。募集的单核细胞随后分泌 IL-27，在正反馈循环中影响 HBE 细胞。经 IL-27 干预后，信号转导和转录激活因子 1（STAT1）磷酸化增加，而 STAT4 和 STAT6 磷酸化减少。
预防性经鼻给予 IL-27 可招募更多分泌 IL-27 的单核细胞到气道，并改变肺中不同的 T 细胞亚群。改善的 Th1 环境有助于通过修复 STAT1 通路而不是 STAT4 通路来缓解 Th2 介导的过敏性哮喘。
