Background Genetic modification of dendritic cells （DCs） has been used as an effective approach to enhance anti-tumor immunity. RNA interference （RNAi）, which can cause the degradation of any RNA in a sequence-spe...Background Genetic modification of dendritic cells （DCs） has been used as an effective approach to enhance anti-tumor immunity. RNA interference （RNAi）, which can cause the degradation of any RNA in a sequence-specific manner, is a post-transcriptional gene silencing mechanism. In this study, small-interfering RNA （siRNA） specific for the li gene was transfected into DCs, and the anti-tumor immunity of li-silenced DCs was assessed. Methods The silencing effect of siRNA was evaluated by Western blotting and real-time PCR analyses. In vitro cytotoxic activity of T cells was evaluated using a Cytotox 96 non-radioactive cytotoxicity assay kit. The time to tumor onset and the tumor volumes were used as reliable indices to assess the anti-tumor immunity in vivo. To further examine the mechanisms underlying the anti-tumor immunity, flow cytometry analysis was used. Results The li expression of DCs was significantly reduced after li siRNA transfection. Significant in vitro anti-tumor ability was exhibited when DCs were co-transfected with li siRNA plus endogenous tumor antigen （P 〈0.05）. Furthermore tumor growth was greatly inhibited when mice were immunized with DCs transfected with li siRNA plus tumor antigen prior to or subsequent to tumor implantation. Flow cytometry analysis in vitro and in vivo indicated that both CD4^= and CD8^＋ T cells were significantly activated in the li siRNA group （P 〈0.05）. Conclusion Silencing of the li gene of DCs may offer a potential approach to enhance DC-based anti-tumor immunity.展开更多
CD74 is a protein whose initial role in antigen presentation was recognized two decades ago. Recent studies have revealed that it has additional functions as a receptor for macrophage migration inhibitory factor and a...CD74 is a protein whose initial role in antigen presentation was recognized two decades ago. Recent studies have revealed that it has additional functions as a receptor for macrophage migration inhibitory factor and as a receptor for an important human pathogen, Helicobacter pylori （H pylon）. The role of CD74 as a receptor is important because after binding of migration inhibitory factor or H pylori, NF-κB and Erkl/2 activation occurs, along with the induction of proinflammatory cytokine secretion. This review provides an up-to-date account of the functions of CD74 and how it might be involved in inflammation and cancer within the gastrointestinal tract.展开更多
Cluster of differentiation 74 （CD74） performs multiple roles in B cells, T cells, and antigen-presenting cells within the immune system; it also participates in ma-jor histocompatibility complex class Ⅱ-restricted ...Cluster of differentiation 74 （CD74） performs multiple roles in B cells, T cells, and antigen-presenting cells within the immune system; it also participates in ma-jor histocompatibility complex class Ⅱ-restricted an-tigen presentation and inflammation. Recently, a role for CD74 in carcinogenesis has been described. CD74 promotes cell proliferation and motility and prevents cell death in a macrophage migration inhibitory factor-dependent manner. Its roles as an accessory signal receptor on the cell surface and the ability to interact with other signaling molecules make CD74 an attrac-tive therapeutic target for the treatment of cancer. This review focuses on the original role of CD74 in the immune system and its emerging tumor-related func-tions. First, the structure of CD74 will be summarized. Second, the current understandings about the expres-sion, cellular localization, molecular mechanisms and signaling pathways of CD74 in immunity and cancer will be reviewed. Third, the examples that suggest CD74 is a promising molecular therapeutic target are reviewed and discussed. Although the safety and ef-fcacy of CD74-targeted strategies are under develop-ment, deeply understanding of the regulation of CD74 will hold promise for the use of CD74 as a therapeutic target and may develop the CD74-targeted therapeutic agents such as neutralized antibody and compounds.展开更多
基金This research was supported by grants from the National Natural Science Foundation of China （No. 30570828 and No. 30471961）.Acknowledgements： The authors deeply appreciate technical assistance from Q. Li and D. Q. Zhang valuble discussion with R. F Ge and help from the experimental Animal Facility technicians for animal care. We thank the International Science Editing for help in editing our manuscript.
文摘Background Genetic modification of dendritic cells （DCs） has been used as an effective approach to enhance anti-tumor immunity. RNA interference （RNAi）, which can cause the degradation of any RNA in a sequence-specific manner, is a post-transcriptional gene silencing mechanism. In this study, small-interfering RNA （siRNA） specific for the li gene was transfected into DCs, and the anti-tumor immunity of li-silenced DCs was assessed. Methods The silencing effect of siRNA was evaluated by Western blotting and real-time PCR analyses. In vitro cytotoxic activity of T cells was evaluated using a Cytotox 96 non-radioactive cytotoxicity assay kit. The time to tumor onset and the tumor volumes were used as reliable indices to assess the anti-tumor immunity in vivo. To further examine the mechanisms underlying the anti-tumor immunity, flow cytometry analysis was used. Results The li expression of DCs was significantly reduced after li siRNA transfection. Significant in vitro anti-tumor ability was exhibited when DCs were co-transfected with li siRNA plus endogenous tumor antigen （P 〈0.05）. Furthermore tumor growth was greatly inhibited when mice were immunized with DCs transfected with li siRNA plus tumor antigen prior to or subsequent to tumor implantation. Flow cytometry analysis in vitro and in vivo indicated that both CD4^= and CD8^＋ T cells were significantly activated in the li siRNA group （P 〈0.05）. Conclusion Silencing of the li gene of DCs may offer a potential approach to enhance DC-based anti-tumor immunity.
基金Supported by The National Institutes of Health Grant K22AI068712, the Texas Board of Higher Educationthe John Sealy Memorial Endowment Fund for Biomedical Research
文摘CD74 is a protein whose initial role in antigen presentation was recognized two decades ago. Recent studies have revealed that it has additional functions as a receptor for macrophage migration inhibitory factor and as a receptor for an important human pathogen, Helicobacter pylori （H pylon）. The role of CD74 as a receptor is important because after binding of migration inhibitory factor or H pylori, NF-κB and Erkl/2 activation occurs, along with the induction of proinflammatory cytokine secretion. This review provides an up-to-date account of the functions of CD74 and how it might be involved in inflammation and cancer within the gastrointestinal tract.
基金Supported by National Science Council of Taiwan,No.NSC 98-2320-B-002-050-MY2 and No.NSC 102-2320-B-039-032-MY3
文摘Cluster of differentiation 74 （CD74） performs multiple roles in B cells, T cells, and antigen-presenting cells within the immune system; it also participates in ma-jor histocompatibility complex class Ⅱ-restricted an-tigen presentation and inflammation. Recently, a role for CD74 in carcinogenesis has been described. CD74 promotes cell proliferation and motility and prevents cell death in a macrophage migration inhibitory factor-dependent manner. Its roles as an accessory signal receptor on the cell surface and the ability to interact with other signaling molecules make CD74 an attrac-tive therapeutic target for the treatment of cancer. This review focuses on the original role of CD74 in the immune system and its emerging tumor-related func-tions. First, the structure of CD74 will be summarized. Second, the current understandings about the expres-sion, cellular localization, molecular mechanisms and signaling pathways of CD74 in immunity and cancer will be reviewed. Third, the examples that suggest CD74 is a promising molecular therapeutic target are reviewed and discussed. Although the safety and ef-fcacy of CD74-targeted strategies are under develop-ment, deeply understanding of the regulation of CD74 will hold promise for the use of CD74 as a therapeutic target and may develop the CD74-targeted therapeutic agents such as neutralized antibody and compounds.
