IL‐10 promotes malignant pleural effusion in mice by regulating TH1‐ and TH17‐cell differentiation and migration

Abstract 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 H 1‐ and T H 17‐cell content in MPE was higher in IL‐10 –/– mice than in WT mice, and IL‐10 deficiency promoted differentiation into T H 1 but not into T H 17 cells. A higher fraction of T H 1 and T H 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 H 1 and T H 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 H 1‐ and T H 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 H 1 cells and upregulated the CXCR3‐CXCL10 signaling pathway that recruits T H 1 and T H 17 cells into MPE, ultimately resulting in decreased MPE formation and longer survival time of mice‐bearing MPE.