Maurizio Ceppi

In response to inflammatory stimulation, dendritic cells (DCs) have a remarkable pattern of differentiation (maturation) that exhibits specific mechanisms to control immunity. Here, we show that in response to Lipopolysaccharides (LPS), several microRNAs (miRNAs) are regulated in human monocyte-derived dendritic cells. Among these miRNAs, miR-155 is highly up-regulated during maturation. Using LNA silencing combined to microarray technology, we have identified the Toll-like receptor/interleukin-1 (TLR/IL-1) inflammatory pathway as a general target of miR-155. We further demonstrate that miR-155 directly controls the level of TAB2, an important signal transduction molecule. Our observations suggest, therefore, that in mature human DCs, miR-155 is part of a negative feedback loop, which down-modulates inflammatory cytokine production in response to microbial stimuli.

T cells. FAP- and CD19-4-1BBL thus represent an off-the-shelf combination immunotherapy without requiring genetic modification of effector cells for the treatment of solid and hematological malignancies.

In response to Toll-like receptor ligands, dendritic cells (DCs) dramatically enhance their antigen presentation capacity by stabilizing at the cell-surface MHC II molecules. We demonstrate here that, in human monocyte-derived DCs, the RING-CH ubiquitin E3 ligase, membrane-associated RING-CH I (MARCH I), promotes the ubiquitination of the HLA-DR beta-chain. Thus, in nonactivated DCs, MARCH I induces the surface internalization of mature HLA-DR complexes, therefore reducing their stability and levels. We further demonstrate that the maturation-dependent down-regulation of MARCH I is a key event in MHC class II up-regulation at the surface of LPS-activated DCs. MARCH I is, therefore, a major regulator of HLA-DR traffic, and its loss contributes to the acquisition of the potent immunostimulatory properties of mature human DCs.

While the extent and impact of horizontal transfers in prokaryotes are widely acknowledged, their importance to the eukaryotic kingdom is unclear and thought by many to be anecdotal. Here we report multiple recent transfers of a huge genomic island between Penicillium spp. found in the food environment. Sequencing of the two leading filamentous fungi used in cheese making, P. roqueforti and P. camemberti, and comparison with the penicillin producer P. rubens reveals a 575 kb long genomic island in P. roqueforti—called Wallaby—present as identical fragments at non-homologous loci in P. camemberti and P. rubens. Wallaby is detected in Penicillium collections exclusively in strains from food environments. Wallaby encompasses about 250 predicted genes, some of which are probably involved in competition with microorganisms. The occurrence of multiple recent eukaryotic transfers in the food environment provides strong evidence for the importance of this understudied and probably underestimated phenomenon in eukaryotes. Horizontal gene transfers are known to play an important role in prokaryote evolution but their impact and prevalence in eukaryotes is less clear. Here, the authors sequence the genomes of cheese making fungi P. roqueforti and P. camemberti, and provide evidence for recent horizontal transfers of a large genomic region.