Th17 and Th9 cells have been demonstrated to possess immune regulatory functions in malignant pleural effusion(MPE). However, whether IL-17 can affect differentiation and function of Th9 cells in MPE remains unknown. The objective of the present study was to explore the impact of IL-17 on the in vivo differentiation of Th9 cells in relation to Th2 cells in a murine model of MPE, and to explore whether IL-17 inhibits MPE formation via IL-9-dependent mechanism. It was found that Th9 and Th2 cells were decreased in MPE from IL-17^(–/–) mice as compared with wild type mice. IL-17 deficiency inhibited Th9 and Th2 cell differentiation via suppressing transcription factors IRF4 and GATA-3, respectively. IL-17 deficiency enhanced MPE formation by promoting angiogenesis and proliferation of pleural tumors, and thus accelerated the death of mice bearing MPE. The in vivo administration of anti-IL-9 neutralizing m Ab accelerated the death of WT mice; whereas administration of exogenous IL-9 improved the survival of IL-17^(–/–) mice. Our data provide the first definitive evidence that IL-17 promotes the differentiation of Th9 and Th2 cells in MPE. Our findings also demonstrate that IL-17 inhibits the formation of MPE and improves the survival of mice bearing MPE via an IL-9–dependent mechanism.
Yong LuHua LinKan ZhaiXiaojuan WangQiong ZhouHuanzhong Shi
Both T helper IL-17-producing cells (Th17 cells) and regulatory T cells (Tregs) have been found to be increased in malignant pleural effusion (MPE). However, the possible imbalance between Th17 cells and Tregs, as well as the association of Th17/Treg and Th1/Th2 cells in MPE remains to be elucidated. The objective of the present study was to investigate the distribution of Th17 cells in relation to Tregs, as well as Th1/Th2 balance in MPE. The number of Th17, Tregs, Th1, and Th2 cells in MPE and peripheral blood was determined by using flow cytometry. The relationship among the number of Th17, Tregs, Th1, and Th2 cells was explored. It was found that the number of Th17, Tregs, Th1, and Th2 cells was all increased in MPE as compared with the corresponding peripheral blood. The number of Th17 cells was correlated negatively with Tregs in MPE, but not in blood. Th17 cells and Th17/Treg ratio were positively, and Tregs were negatively, correlated with Th1 cells, but not with either Th2 cells or Th1/Th2 ratio in MPE. This study supports earlier data that both Th17 cells and Treg are present at higher frequencies in MPE than in the autologous blood. For the first time, we show that Th17/Treg imbalance exists in MPE.
