The regulation of CD4+ T cell immune responses toward Th2 cell development by prostaglandin E2

As an important immune mediator, PGE2 plays an important role in the immune tolerance, autoimmune diseases, immune regulation and tumor immunotolerance. PGE2 is considered to be a promising candidate for the control of the immune diseases. To further understand the immuno-modulating effects of PGE2 on CD4+ T cells, in vitro investigation was conducted in the present study. The results showed that PGE2 inhibited the proliferation of T cells in vitro in a dose-dependent manner. Gene expression profiling showed that 1716 genes were down regulated and 73 genes were up regulated with a change of 1.5 fold. Several signal transduction pathways were involved, such as TNF-α and NF-kB signaling pathway, T cell receptor signaling pathway, IL-2 signaling pathway, and MAPK pathway. The results showed that PGE2 inhibited IFN-γ, TNF-α and IL-4 production by CD4+ T cells 24 h after cell culture. A comparison between IFN-γ and IL-4 production showed that PGE2 enhanced the relative ratio of IL-4 to IFN-γ in CD4+ T cells culture, and regulated CD4+ T cells toward Th2 cell development. The results of the present study indicated that PGE2 has the potential to treat Th1-mediated inflammatory diseases by regulating CD4+ T cells toward Th2 cell immune response.

► In this study we address the role of PGE2 as a modulator of the immune response in vitro. ► PGE2 inhibits the proliferation of CD4+ T cells in a dose-dependent manner. ► PGE2 down-regulates the expression of immune regulation genes in CD4+ T cells. ► PGE2 inhibited IFN-γ and TNF-α production by CD4+ T cells 24 h and 48 h after cell culture respectively. ► PGE2 enhanced the IL-4/IFN-γ ratio in CD4+ T cells culture, and regulated CD4+ T cells toward Th2 polarization.