Ligand activation of PPAR d decreases the abundant cbx1 proteins required formation sahf cell expression of VEGF in colon cancer cells. These findings indicate that, PPAR d may inhibit tumor growth by inducing differentiation, attenuating cell proliferation and VEGF-mediated angiogenesis in the pathogenesis of colon cancer, and facilitate the tumor sensitivity to bevacizumab. These results support the rationale for developing PPAR d agonists for prevention and/or treatment of colon cancer. For human pDC, it has been demonstrated that the level of IFN-a production by pDC is controlled by distinct cytokines. We therefore hypothesized that cytokines could promote the weak pDC responses to FMDV and aimed to characterize the impact of several cytokines secreted by T helper, myeloid and stromal cells on IFN-a responses and pDC survival. Stimulatory effects were found with haematopoietic cytokines, Th1 and Th2 cytokines, type I IFN and only one of the analysed pro-inflammatory cytokines. Anti-inflammatory interleukin -10 was the only suppressive cytokine identified. The present study confirms and elaborates on the important impact of cytokines on pDC activation and survival. High level of IFN-a production did not always relate to the high number of surviving pDC indicating that other factors such as priming effects are mediating the effects. An example for this are the known effects of type I IFNs on the expression of IRF7, a key transcription factor for IFN-a. We also demonstrated that the effect of cytokines is not identical when CpG is compared to FMDV stimulation. This is not surprising, considering that cytokines may modulate pDC elements, which indirectly influence IFN-a responses such as uptake receptors or the antiviral status of the cells. For example, entry of FMDV requires specific integrins at the cell surface while CpG utilizes a multilectine receptor, DEC-205. It is also possible that the differences are caused by the fact that pDC respond to CpG via toll-like receptor 9 and FMDV via TLR7. Compared to CpG, FMDV is a very inefficient stimulator of pDC even in the presence of promoting cytokines. There are several possible explanations for this. First, the virus seems inefficient in attaching and entering pDC, and this can be improved by complexing it with specific antibodies which promote FccRII-mediated uptake. We know from previous work that pDC activation by FMDV is not influenced by cell culture adaptation to heparin sulphate receptors. Second, after endocytosis of FMDV by pDC viral RNA might by delivered mostly to the cytosol. As FMDV cannot efficiently replicate in pDC, little RNA will be available for TLR7 triggering. Third, viral inhibitors of the IFN system such as Lpro might prevent pDC activation. Future studies are required to address this issue but it appears that in vivo pDC are activated by FMDV, resulting in a transient early systemic IFN-a response, indicating that pDC represent a relevant cell type during FMDV infection. In general terms, our study support the concept that pDC are regulated at various steps of the innate and adaptive immune response by the cytokine network. The inflammatory cytokines tested were not able to promote activation of pDC with the exception of TNF-a, which enhanced the levels of IFN-a in response to FMDV but not CpG. A possible explanation for this could be antiviral effects controlling the level of viral proteins known to interfere with the IFN system such as Lpro of FMDV. The observation that IL-17A did not influence pDC responses would relate to the fact that this cytokine is typically associated with bacterial infections for which strong pDC responses are less relevant. It is also understandable that during strong inflammatory cytokine responses often associated with tissue damage an additional potentiation of IFN-a responses could be detrimental. In contrast, the two hematopoietic cytokines tested were able to enhance pDC responses.