Interplay of Th1 and Th17 Cells in Murine Models of Malignant Pleural Effusion

Abstract

In mouse models of MPE, IFN-γ inhibited Th17-cell differentiation, whereas IL-17 inhibited Th1-cell differentiation. IL-17 inhibited the formation of MPE and improved the survival of mice bearing MPE; in contrast, IFN-γ promoted MPE formation and mouse death.

Interleukin-17 inhibits development of malignant pleural effusion via interleukin-9-dependent mechanism

“…These data indicate that both endogenous and exogenous IL-17 are capable of inhibiting the development of MPE. As reported in our previous paper (Lin et al, 2014), expressions of both CD34 and Ki-67 in pleural tumors are increased in IL-17 / mice. We extended these work and further observed that intraperitoneal injection of anti-IL-17 mAb in WT mice significantly increased the numbers of both CD34 + ( Figure 2A) and Ki-67 + cells (P<0.01) ( Figure 2B); while intraperitoneal injection of rmIL17 in IL-17 …”

“…In the previous study (Lin et al, 2014), we have demonstrated that more pleural tumor foci and bloody MPE are found in IL-17 / mice as compared with WT mice 14 days after intrapleural injection of LLC cells. Here once again we confirmed that radiotracer uptake was significantly increased on FDG-PET scanning in IL-17 / mice ( Figure 1A).…”

“…More recently, we have demonstrated that IL-17 deficiency promotes angiogenesis and proliferation activity of pleural tumors as well as pleural vascular permeability, and thus promotes MPE formation (Lin et al, 2014). The finding that IL-17 deficiency accelerates the death of mice bearing MPE observed in the animal study (Lin et al, 2014) is consistent with the finding that the accumulation of Th17 cells in MPE predicts improved patient survival in the human study (Ye et al, 2010). Consistent with our previous findings (Lin et al, 2014), we confirmed that IL-17 deficiency promoted MPE formation by enhancing the angiogenesis and proliferation of pleural tumors, and that in vivo administration of anti-IL-17 mAb in WT mice was able to promote MPE formation by increasing tumor angiogenesis and proliferation, while in vivo administration of rmIL-17 in IL-17 / mice was able to inhibit MPE formation by diminishing tumor angiogenesis and proliferation.…”

“…On the other hand, Tregs inhibit the generation and differentiation of Th17 cells via a latency-associated peptide-dependent mechanism (Ye et al, 2011). More recently, we have demonstrated that IL-17 deficiency promotes angiogenesis and proliferation activity of pleural tumors as well as pleural vascular permeability, and thus promotes MPE formation (Lin et al, 2014). The finding that IL-17 deficiency accelerates the death of mice bearing MPE observed in the animal study (Lin et al, 2014) is consistent with the finding that the accumulation of Th17 cells in MPE predicts improved patient survival in the human study (Ye et al, 2010).…”

“…Our previous studies revealed that both Th17 and Th9 cells are increased in MPE which is promoted by local proinflammatory cytokines, and these Th cells exert an important immune regulation on lung cancer cells in tumor environment (Ye et al, 2010(Ye et al, , 2012b. More recently, we have demonstrated that IL-17 deficiency promotes angiogenesis and proliferation activity of pleural tumors as well as pleural vascular permeability, and thus promotes MPE formation in the animal models of MPE using IL-17 / mice (Lin et al, 2014). In the present study, we were prompted to explore the impact of IL-17 on the 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.…”