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 1L-17-/- mice as compared with wild type mice. IL-17 deficiency inhibited Th9 and Th2 cell differentiation via suppressing transcription faclLors IRF4 and GATA-3, respectively. IL-17 deficiency enhanced MPE formation by promoting angiogenesis and proliferation of pleurai tumors, and thus accelerated the death of mice bearing MPE. The in vivo administration of anti-IL-9 neutralizing mAb accelerated the death of WT mice; whereas administration of exoge- nous IL-9 improved the survival of IL-17-/- mice. Our data provide the first definitive evidence that IL-17 promotes the differ- entiation 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 （Thl7 cells） and regulatory T cells （Tregs） have been found to be increased in malignant pleural effusion （MPE）. However, the possible imbalance between Thl7 cells and Tregs, as well as the association of.Thl7/Treg and Thl/Th2 cells in MPE remains to be elucidated. The objective of the present study was to investigate the distribution of Th 17 cells in relation to Tregs, as well as Thl/Th2 balance in MPE. The number ofThl7, Tregs, Thl, and Th2 cells in MPE and peripheral blood was determined by using flow cytometry. The relationship among the number of Thl7, Tregs, Thl, and Th2 cells was explored. It was found that the number of Thl7, Tregs, Thl, and Th2 cells was all increased in MPE as compared with the corresponding peripheral blood. The number of Thl7 cells was correlated negatively with Tregs in MPE, but not in blood. Thl7 cells and Thl7/Treg ratio were positively, and Tregs were negatively, correlated with Thl cells, but not with either Th2 cells or Th1/Th2 ratio in MPE. This study supports earlier data that both Thl7 cells and Treg are present at higher frequencies in MPE than in the autologous blood. For the first time, we show that Thl7/Treg imbalance exists in MPE.
Background： lnterlcukin （IL）-27 has been reported to have anti-proliferate and anti-angiogenic activities on cancer cells. However, the involvement of IL-27 in malignant pleural effusion （MPE） remains unknown. Thus, in this research, we compared the immune functions of IL-27, interferon （IFN）-γ, and IL-17 on lung cancer cells and revealed the regulatory mechanism of IL-27 in MPE. Methods： The distribution ofl L-27 in both MPE and blood was evaluated by enzyme-linked immunosorbent assay and flow cytometry. The expressions otcytokine receptors and the levels of the phosphorylated signal transducer and activator of transcription （STAT） signalings were detected by flow cytometry. As well as the effects of proliferation, apoptosis, migration, and adherent activity of IL-27, IFN-γ, and IL-17 on lung cancer cells were also explored. Results： The expression of IL-27 was increased in M PE when compared with blood （ 147.3 ± 25. 1 pg/ml vs. 100.3 ± 13.9 pg/ml, P = 0.04）. IL-27 was noted to suppress both proliferation （18.33 ±0.21 vs. 27.77 ±0.88, P = 0.0005） and migration （1.82 ±0.44 vs. 3.13 ±0.07, P = 0.04） of A549 cells, but obviously prornoted apoptosis of A549 cells （9.47 ±1.14 vs. 4.96 ±0.17, P = 0.02） by activating STAT1 signaling. Interestingly, IL-27 played totally opposite effects on A549 cells by activating STAT3 pathway. Moreover, IL-27 exerted different intercellular adherent activities ofA549 cells to pleural mesothelial cell monolayer by activating different STAT signalings. Conelusions： IL-27 might exert an important immune regulation on lung cancer cells in human pleural malignant environment.
Shi LiWen-Jie YouJian-Chu ZhangQiong ZhouHuan-Zhong Shi
