Qiu Shi-Lin, Duan Min-Chao, Liang Yi, Tang Hai-Juan, Liu Guang-Nan, Zhang Liang-Ming, Yang Chao-Mian
Department of Respiratory Medicine, The First Affiliated Hospital of Guangxi Medical University , Nanning , China.
Department of Respiratory Medicine, The Fifth Affiliated Hospital of Guangxi Medical University and The First People's Hospital of Nanning , Nanning , China.
Front Immunol. 2016 Dec 5;7:553. doi: 10.3389/fimmu.2016.00553. eCollection 2016.
IFN-γ-producing CD4 T (Th1) cells and IL-17-producing CD4 T (Th17) cells play a critical role in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the immune regulation between Th1 and Th17 cells remains unclear. Previous studies have demonstrated that interleukin-27 (IL-27)/WSX-1 exerted pro- or anti-inflammatory effects in many acute inflammatory diseases by modulating T cell-mediated immune response, but little was known about its role in chronic inflammatory disease, especially in smoking-related lung diseases. Considering IL-27 is an important regulator in T lymphocytes immune responses and was found markedly increased in patients with COPD, we hypothesized that IL-27/WSX-1 may exert immuno-regulatory effects on the differentiation of Th1 and Th17 cells in smoking-related COPD. In this study, we aimed to evaluate the expression of IL-27 in patients with COPD and explore the role of IL-27/WSX-1 on Th1 and Th17 cells differentiation in a smoking mouse model of emphysema. We found that elevated expression of IL-27 was associated with increased proportion of Th1 cells and Th17 cells in patients with COPD and demonstrated parallel findings in cigarette smoke-exposed mice. In addition, cigarette smoke exposure upregulated the expression of IL-27R (WSX-1) by naive CD4 T cells in mice. , IL-27 significantly augmented the secretion of IFN-γ by naive CD4 T cells a T-bet, p-STAT1, and p-STAT3-dependent manner, but inhibited the production of IL-17 by a ROR-γt and p-STAT1-dependent way. Furthermore, anti-IL27 treatment dramatically decreased the expression of IFN-γ-producing CD4 T cells in cigarette smoke-exposed mice. These findings proposed that IL-27 has functions for promoting the expression of Th1 cells but inhibiting the expression of Th17 cells and IL-27 neutralization-attenuated Th1-mediated inflammation , suggesting targeting IL-27/WSX-1 may provide a new therapeutic approach for smoking-related COPD.
产生干扰素-γ的CD4 T（Th1）细胞和产生白细胞介素-17的CD4 T（Th17）细胞在慢性阻塞性肺疾病（COPD）的发病机制中起关键作用。然而，Th1细胞和Th17细胞之间的免疫调节仍不清楚。先前的研究表明，白细胞介素-27（IL-27）/WSX-1通过调节T细胞介导的免疫反应在许多急性炎症性疾病中发挥促炎或抗炎作用，但对其在慢性炎症性疾病中的作用知之甚少，尤其是在与吸烟相关的肺部疾病中。鉴于IL-27是T淋巴细胞免疫反应中的重要调节因子，且在COPD患者中发现其明显升高，我们推测IL-27/WSX-1可能对与吸烟相关的COPD中Th1和Th17细胞的分化发挥免疫调节作用。在本研究中，我们旨在评估COPD患者中IL-27的表达，并在肺气肿吸烟小鼠模型中探讨IL-27/WSX-1对Th1和Th17细胞分化的作用。我们发现，COPD患者中IL-27表达升高与Th1细胞和Th17细胞比例增加有关，且在暴露于香烟烟雾的小鼠中也有类似发现。此外，香烟烟雾暴露上调了小鼠中幼稚CD4 T细胞的IL-27R（WSX-1）表达。IL-27以T-bet、p-STAT1和p-STAT3依赖的方式显著增强幼稚CD4 T细胞分泌干扰素-γ，但以ROR-γt和p-STAT1依赖的方式抑制白细胞介素-17的产生。此外，抗IL27治疗显著降低了暴露于香烟烟雾的小鼠中产生干扰素-γ的CD4 T细胞的表达。这些发现表明，IL-27具有促进Th1细胞表达但抑制Th17细胞表达的功能，且IL-27中和可减轻Th1介导的炎症，提示靶向IL-27/WSX-1可能为与吸烟相关的COPD提供一种新的治疗方法。
