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

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-gamma 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.