Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Eur J Immunol. 2019 Apr;49(4):653-665. doi: 10.1002/eji.201847685. Epub 2019 Feb 12.
The role of IL-10 in malignant pleural effusion (MPE) remains unknown. By using murine MPE models, we observed that an increase in pleural IL-10 was a significant predictor of increased risk of death. We noted that T 1- and T 17-cell content in MPE was higher in IL-10 mice than in WT mice, and IL-10 deficiency promoted differentiation into T 1 but not into T 17 cells. A higher fraction of T 1 and T 17 cells in the MPE of IL-10 mice expressed CXCR3 compared with WT mice. We also demonstrated that Lewis lung cancer and colon adenocarcinoma cells secreted large amounts of CXCL10, a ligand of CXCR3, which induced the migration of T 1 and T 17 cells into the MPE, and IFN-γ could promote this signaling cascade. Furthermore, intrapleural injection of mice with CXCL10-deficient tumor cells led to decreased T 1- and T 17-cell content in MPE, increased MPE volume, and reduced survival of MPE-bearing mice. Taken together, we demonstrated that IL-10 deficiency promoted T-cell differentiation into T 1 cells and upregulated the CXCR3-CXCL10 signaling pathway that recruits T 1 and T 17 cells into MPE, ultimately resulting in decreased MPE formation and longer survival time of mice-bearing MPE.
白细胞介素-10（IL-10）在恶性胸腔积液（MPE）中的作用尚不清楚。通过使用小鼠 MPE 模型，我们观察到胸腔内 IL-10 的增加是死亡风险增加的一个重要预测因素。我们注意到，MPE 中 T1 和 T17 细胞的含量在 IL-10 小鼠中高于 WT 小鼠，并且 IL-10 缺乏促进向 T1 分化而不是 T17 细胞分化。与 WT 小鼠相比，IL-10 小鼠 MPE 中的 T1 和 T17 细胞中更高比例的细胞表达 CXCR3。我们还证明了 Lewis 肺癌和结肠腺癌细胞大量分泌 CXCL10，这是 CXCR3 的配体，可诱导 T1 和 T17 细胞迁移到 MPE 中，IFN-γ 可促进这种信号级联反应。此外，向 MPE 小鼠胸腔内注射缺乏 CXCL10 的肿瘤细胞，可导致 MPE 中 T1 和 T17 细胞含量减少、MPE 体积增加以及 MPE 荷瘤小鼠的生存时间减少。综上所述，我们证明了 IL-10 缺乏促进 T 细胞向 T1 细胞分化，并上调了招募 T1 和 T17 细胞进入 MPE 的 CXCR3-CXCL10 信号通路，最终导致 MPE 形成减少和 MPE 荷瘤小鼠的生存时间延长。
