...prolonged DC survival and an increase in T cell priming capability. Our findings reveal novel aspects of the molecular signaling triggered by LPS in DCs and identify a new role for CD14: the regulation of the DC life cycle through NFAT activation.

...nce of TLR stimuli able to induce Th1 responses STAT-1 was activated. This observation strongly suggested that the molecules selectively produced by DC in presence of Th1 stimuli and not in presence of Th2 stimuli were type I IFNs and that these cytokines were presumably required for NK cell activat...

...riments in human monocyte-derived DCs (MDDCs) with the dual aim of generating relevant knowledge and data on (i) the transcriptional regulation of DC differentiation, and (ii) the safe and rationale in vitro manipulation of gene expression in DCs. One of the two different approaches that have b...

...hagocytisable Dectin-1 ligands are much more potent agonists than smaller ones. This is the first example of a bona fide signalling pathway from a cell surface innate receptor other than a TLR. We will continue to study innate signalling pathways in dendritic cells. Our focus will be on TLR-indep...

...skin site of mice. In particular, attention has been focussed on the recruitment of distinct subsets of DC to skin. This work, which is being performed in collaboration with PowderMed, a former SME now owned by Pfizer, may lead to the development of more targeted strategies to induce distinct T cell...

Data has been obtained on the activation of human DC by Toll like receptor ligands (TLR-L) that modulates the lipid biosynthetic pathway, resulting in enhanced recognition of CD1d-associated lipids by iNKT cells. DC derived soluble factors further increase CD1d-restricted iNKT cell activation, as de...

... the role of ICOShi regulatory T cells in the intestine in steady state conditions and (3) the role of intestinal flora in the development of these cells using axenic mice. In parallel, we are testing whether the population of natural regulatory T cells (CD25+) control immune responses by acting on ...

Our laboratory has obtained data on the role of DC-derived cytokines in NK cell production of IFN-gamma.

...lity at inducing T cell activation. Indeed we established that the mDC/pDC cross-talk has a functional effect on T cell activation. In fact the mDC/pDC cooperation event is able to significantly increase the ability of these cells to drive the proliferation and IFN? production by alloreactive T cell...

...co-cultured pDC. On the other hand type I interferons produced by CpG-activated pDCs is required for activation of the mDC. We also observed a strong synergistic response of both cell types, using limiting conditions of stimulus on co-cultured mDCs and pDCs. The study on the response of human MoDC...

Our lab has obtained data on maturation stimuli for GMP-grade DC.

...ur lab has generated data on receptors on dendritic cells necessary for capture of exosomes. In 2007, we have finalized analysis of the receptors on DCs responsible for capture of exosomes secreted by mature DCs. We have shown that expression of LFA-1, but not of Mac-1, integrin, on DCs is required ...

...rin. Tumors secreting the exosome-bound antigen grow slower than tumors secreting soluble OVA, because they induce activation of OVA-specific CD8+ T cells into killer cells. In addition, inducing in vivo secretion of the C1C2-coupled antigen by DNA vaccination induces prevention against subsequent t...

...ween human monocyte derived DCs (MDDC), generated in the presence of GM-CSF and IL-4 (IL-4 DC), and antigen-stimulated circulating gamma delta T lymphocytes, bearing the Vgamma2 TCR. Co-cultures of IFN-DCs with zoledronate-stimulated gamma delta T lymphocytes were also performed. gamma delta T-cell ...

...bLf, whose immunomodulant properties are now recognized, on MDDC differentiation/activation. We found that bLF interferes with the activation of MD-DC induced by different TLR agonists, but not by T cell mediated signals. Although bLF did not significantly influence monocyte differentiation in DCs,...

...between TLRs induce different functional states of DCs that favour different T cell effector phenotypes. Moreover, a further characterization of the molecular mechanisms underlying CCL2 regulation, will be also performed; - defining the role of selected miR on the differentiation/activation of MDDC...

...of both cell populations will be performed, and in particular it will be analyzed: (a) the capacity of virus-exposed DCs to recruit resting gamma-delta T cells; (b) the role of activated lymphocytes in controlling HIV-1 replication in DCs; (c) whether active virus replication in these cells is ne...

...t CTL expansion, effector function and CTL memory. In contrast, CTL that have received suboptimal stimulation fail to undergo extensive expansion. Nevertheless these arrested CTL persist long term and acquire memory function in the absence of further cell division. Thus our data demonstrate that CTL...

...he way antigens should be introduced in DCs and how long after stimulation they should be used during vaccination application. We have also initiated studies on the impact of dsRNA on the regulation of translation and the functional response of DCs (IFN production). We have now demonstrated that DC...

... TLR9. We will continue to use DC activation in vitro and, in particular, DC cytokine production as an assay to dissect innate pathways involved in DC activation. In parallel, we will continue to compare effector T cell instruction by DC activated via distinct innate receptors.