The Transcription Factor E2f1 Inhibited The Maturation Of Dendritic Cells

Dendritic cell (DC) has been considered to be the most potent professional antigen-presenting cell (APC) that initiates primary immune responses. Its ability to stimulate and regulate T- and B-cell responses makes DC ideally can be served as an adjuvant for cancer immunotherapy. DC also involved in the pathogenesis of graft versus host disease or host versus graft disease after transplantation as well as immunization against viral infections and immuno-suppression in autoimmune diseases. One possible reason for losing effective anti-tumor immunity is that tumor antigens can not be appropriately presented by DC. Thus, based on the research on genes changed during DC maturation and the related regulated mechanism, we can find some important information and then restore the ability of potent Ag presenting of DC in cancer.it is widely recognized that E2F1 invovles in regulation of cell cycle and cell proliferation through promoting G0/G1 transition and the process of apoptosis. Recently, E2F1 has been shown to regulate a wide range of genes in response to inflammatory stimulation of macrophages and to contribute to T cell activation in response to pathogens, implicating an extensive immunological role for E2F1. However, it is unclear whether E2F1 has any effect on DC development and differenciation.In present study, we showed that the expression patterns of TLRs dynamically changed during DC maturation upon LPS induction. The level of E2F1 expression was transiently downregulated in the course of LPS-induced maturation of both human monocyte-derived dendritic cells and a mouse DC cell line, DC2.4. Knockdown of E2F1 by siRNA in DC2.4 cells resulted in both phenotypic and functional maturation, even without LPS treatment. Conversely, ectopic overexpression of E2F1 suppressed LPS-induced maturation of DC2.4 cells. Furthermore, knockdown of E2F1 caused the activation of several major signaling pathways known to be activated in the course of DC maturation, including Erk1/2, NF-κB and PI3K/Akt, suggesting that E2F1 may be involved in regulating multiple signaling pathways in dendritic cells. Finally, the alternation by E2F1 on phenotypic maturation was confirmed with bone marrow-derived DCs from E2F1-KO mice. Overall, our data demonstrate for the first time that E2F1 is a critical regulator of dendritic cell maturation.