轉(zhuǎn)錄因子E2F1對樹突狀細胞成熟的抑制作用.pdf

1、中國科學技術(shù)大學碩士學位論文轉(zhuǎn)錄因子E2F1對樹突狀細胞成熟的抑制作用姓名：王艷申請學位級別：碩士專業(yè)：細胞生物學指導教師：肖衛(wèi)華20100112Abstract III Abstract Dendritic cell (DC) has been considered to be the most potent professional antigen-presenting cell (APC) that initiates prima

2、ry 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

3、 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 tum

4、or 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 abi

5、lity 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

6、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 E2F

7、1. 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. T

8、he 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

9、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 ac