http://repub.eur.nl/res/aut/28795/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/35030/ 2012-01-01T00:00:00Z Interleukin-10 (IL-10) plays an indispensable role in mucosal tolerance by programming dendritic cells (DCs) to induce suppressor Th-cells. We have tested the modulating effect of L. lactis secreting human IL-10 (L.lacti s IL-10) on DC function in vitro. Monocyte-derived DC incubated with L.lacti s IL-10 induced effector Th-cells that markedly suppressed the proliferation of allogenic Th-cells as compared to L. lactis. This suppressive effect was only seen when DC showed increased CD83 and CD86 expression. Furthermore, enhanced production of IL-10 was measured in both L.lacti s IL-10 -derived DC and Th-cells compared to L. lactis-derived DC and Th-cells. Neutralizing IL-10 during DC-Th-cell interaction and coculturing L.lacti s IL-10 -derived suppressor Th-cells with allogenic Th-cells in a transwell system prevented the induction of suppressor Th-cells. Only 130pg/mL of bacterial-derived IL-10 and 40 times more exogenously added recombinant human IL-10 were needed during DC priming for the generation of suppressor Th-cells. The spatially restricted delivery of IL-10 by food-grade bacteria is a promising strategy to induce suppressor Th-cells in vivo and to treat inflammatory diseases. http://repub.eur.nl/res/pub/23425/ 2011-05-25T00:00:00Z One of the most important and defining processes during development is the pattern formation of the various compartments in embryos. In an effort to discover the participants involved in regulating compartment size, we identified, in Danio rerio (zebrafish) embryos, the ankyrin repeat and SOCS box-containing protein 11 (d-asb11) gene. We first showed that d-Asb11 is a key mediator of Delta-Notch Signaling, acting at the level of DeltaA ubiquitylation, important in fine-tuning the lateral inhibition gradients between DeltaA and Notch. We, then, isolated a zebrafish having a germline deletion of the d-Asb11 cullin box subdomain and showed that this deletion resulted in loss of d-Asb11 activity. As a consequence, the animals were defective for Notch signaling and proper cell fate specification within the neurogenic regions of zebrafish embryos. We also provided evidence that d-Asb11 is important in maintaining myogenic proliferation in the stem cell compartment of zebrafish embryos and muscle regenerative responses in adult animals. This finding is supported by the highly specific d-Asb11 expression found in proliferating satellite cells in zebrafish muscle. In addition, we have applied immunoaffinity chromatograpy followed by tandem mass spectrometry to identify human ASB11 interacting proteins. The data confirmed the role of ASB11 as a substrate-recognition that targets proteins for ubiquitylation and proteasomal degradation via the canonical ECS ubiquitin ligase complex. Altogether our results provide important new insight on the action and function of ASB11 in regulating progenitor compartment expansion, possibly by controlling protein levels in the cells.