IL-27 mediates anti-inflammatory effect in cigarette smoke induced emphysema by negatively regulating IFN-γ producing cytotoxic CD8+T cells in mice
IL-27 mediates anti-inflammatory effect in cigarette smoke induced emphysema by negatively regulating IFN-γ producing cytotoxic CD8+T cells in mice
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IL-27 通过负调节小鼠体内产生细胞毒性 CD8 T 细胞的 IFN-γ 介导香烟烟雾诱发肺气肿的抗炎作用
DOI：
10.1002/eji.202049076
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发表时间：
2021-10-24
影响因子：
5.4
通讯作者：
Duan，Min-Chao
中科院分区：
文献类型：
--
作者：
Qiu，Shi-Lin;Sun，Qi-Xiang;Duan，Min-Chao
CD 8 +T淋巴细胞介导的慢性气道炎症参与了慢性阻塞性肺病（COPD）的发病机制。破译由CD 8 +T细胞协调的慢性炎症的指纹可能允许开发COPD管理的新方法。在此，在COPD患者和香烟烟雾暴露小鼠中评估了IL-27和IFN-γ+ CD 8 + Tc 1细胞的表达。评估了骨髓来源的树突状细胞（mDC）响应香烟烟雾提取物（CSE）产生的IL-27。探讨了IL-27在IFN-γ+ CD 8 + Tc 1细胞中的作用。我们证明，在吸烟小鼠肺气肿模型中，IL-27升高伴随着过度的IFN-γ+ CD 8 + Tc 1反应。我们注意到，肺树突状细胞是慢性香烟烟雾暴露期间IL-27的主要来源之一。此外，CSE在体外直接诱导mDC产生IL-27。IL-27以不依赖于STAT 1和STAT 3的方式负调节从香烟烟雾暴露小鼠中分离的IFN-γ+ CD 8 + Tc 1细胞的分化。全身给予重组IL-27可减弱香烟烟雾暴露后期的IFN-γ+ CD 8 + Tc 1应答。我们的研究结果发现，IL-27在慢性香烟烟雾暴露的晚期负性调节IFN-γ+ CD 8 + Tc 1反应，这可能为吸烟相关的COPD/肺气肿的抗炎治疗提供新的策略。
Chronic airway inflammation mediated by CD8+T lymphocytes contributes to the pathogenesis of Chronic obstructive pulmonary disease (COPD). Deciphering the fingerprint of the chronic inflammation orchestrated by CD8+T cells may allow the development of novel approaches to COPD management. Here, the expression of IL‐27 and IFN‐γ+CD8+Tc1 cells were evaluated in patients with COPD and in cigarette smoke‐exposed mice. The production of IL‐27 by marrow‐derived dendritic cells (mDCs) in response to cigarette smoke extract (CSE) was assessed. The role of IL‐27 in IFN‐γ+CD8+Tc1 cells was explored. We demonstrated that elevated IL‐27 was accompanied by an exaggerated IFN‐γ+CD8+Tc1 response in a smoking mouse model of emphysema. We noted that lung dendritic cells were one of the main sources of IL‐27 during chronic cigarette smoke exposure. Moreover, CSE directly induced the production of IL‐27 by mDCs in vitro. IL‐27 negatively regulated the differentiation of IFN‐γ+CD8+Tc1 cells isolated from cigarette smoke‐exposed mice in a STAT1‐ and STAT3‐independent manner. Systemic administration of recombinant IL‐27 attenuated IFN‐γ+CD8+Tc1 response in the late phase of cigarette smoke exposure. Our results uncovered that IL‐27 negatively regulates IFN‐γ+CD8+Tc1 response in the late stage of chronic cigarette smoke exposure, which may provide a new strategy for the anti‐inflammatory treatment of smoking‐related COPD/emphysema.