Interplay Of Th1and Th17Cells In Murine Models Of Malignant Pleural Effusion

Rationale IFN-γ-producing CD4+T (Th1) cells and IL-17-producing CD4+T (Th17) cells have been found to be involved in multiple malignancies; however, the reciprocal relationship between Thl and Th17cells in malignant pleural effusion (MPE) remain to be elucidated.Objectives To explore the differentiation and immune regulation of Th1and Th17cells in the development of MPE in a murine model.Methods The distribution and differentiation of Th1and Th17cells in MPE were investigated in IFN-γ-/-, IL-17-/-, and wild type mice. The effects of Thl and Th17cells on the development of MPE and the survival of mice bearing MPE were also investigated.Measurements and Main Results We have demonstrated that increased Th1and Th17cells could be found in MPE as compared with blood and spleen. Compared with wild type mice, Th17cells were markedly augmented in MPE from IFN-γ-/-mice, and improved survival could be seen in IFN-γ mice. Thl cell numbers were also elevated in MPE from IL-17-/-mice, and decreased survival could be seen in IL-17-/-mice. The in vitro experiments showed that IFN-y deficiency promoted Th17cell differentiation via suppressing STAT3pathway, and that IL-17deficiency promoted Thl cell differentiation via suppressing STAT1pathway.Conclusions IFN-y inhibited Th17cell differentiation while IL-17inhibited Thl cell differentiation in a mouse model of MPE. IL-17inhibited the formation of MPE and improved the survival of mice bearing MPE; in contrast, IFN-y promoted MPE formation and mouse death.