Organisation of elections beyond territory and membership

In this EUDO CITIZENSHIP Comparative Report, the author explores the links between this situation and the most important international features of electoral law: out-of-country voting; voting by foreigners; international election observation; transnational elections. After examining how international hard and soft law addresses these issues, he sustains the paradox that out-of-country voting is the only one directly linked to the information society, since it needs easy access to information without borders, whereas voting by foreigners is still based on territory, and while international election observation results from democratisation and transnational elections from supranational integration

A type I interferon autocrine–paracrine loop is involved in Toll-like receptor-induced interleukin-12p70 secretion by dendritic cells

Dendritic cells (DC) produce interleukin-12 (IL-12) in response to Toll-like receptor (TLR) activation. Two major TLR signaling pathways participate in the response to pathogens: the nuclear factor-κB (NF-κB)–dependent pathway leading to inflammatory cytokine secretion including IL-12 and the interferon (IFN)-dependent pathway inducing type I IFN and IFN-regulated genes. Here we show that the two pathways cooperate and are likely both necessary for inducing an optimal response to pathogens. R-848/Resiquimod (TLR7 ligand in the mouse and TLR7/8 ligand in human) synergized with poly(I:C) (TLR3 ligand) or lipopolysaccharide (LPS; TLR4 ligand) in inducing high levels of bioactive IL-12p70 secretion and IFN-β mRNA accumulation by mouse bone marrow–derived DC (BM-DC). Strikingly, IL-12p70 but not IL-12p40 secretion was strongly reduced in BM-DC from STAT1−/− and IFNAR−/− mice. STAT1 tyrosine-phosphorylation, IL-12p35, and IFN-β mRNA accumulation were strongly inhibited in IFNAR−/− BM-DC activated with the TLR ligand combinations. Similar observation were obtained in human TLR8-expressing monocyte-derived DC (moDC) using neutralizing anti-IFNAR2 antibodies, although results also pointed to a possible involvement of IFN-λ1 (also known as IL-29). This suggests that TLR engagement on DC induces endogenous IFNs that further synergize with the NF-κB pathway for optimal IL-12p70 secretion. Moreover, analysis of interferon regulatory factors (IRF) regulation in moDC suggests a role for IRF7/8 in mediating IRF3-independent type I IFN and possibly IL-12p35 synthesis in response to TLR7/8

Activation des cellules dendritiques par les récepteurs de la famille Toll (implication d'une boucle autocrine/paracrine d'interféron de type I dans la production d'interleukine-12)

La cellule dendritique (DC) est une cellule présentatrice d'antigène à l'interface entre immunité innée et adaptative. Selon son origine, elle exprime différents récepteurs de la famille Toll (TLR) reconnaissant des structures moléculaires conservées des pathogènes. Nous montrons que 1/ l'activation des DC myéloïdes in vitro par les TLR-7/-8 entre en synergie avec le TLR-3 et le TLR-4 pour induire deux cytokines clés : l'interleukine-12 (IL-12) reliant immunité innée et adaptative et les interférons (IFN) de type I initiateurs de la réponse anti-virale, 2/ la sécrétion d'IL-12p70 biologiquement active est dépendante d'une boucle autocrine d'IFN-a/b régulant l'accumulation de l'ARN messager d'IL-12p35, 3/ La sécrétion endogène d'IFN-[lambda] induite par les TLR-3,-4 et -8 pourrait aussi participer à l'induction d'IL-12p70 mais contrairement aux TLR-3 et -4, le TLR-8 active une voie de signalisation indépendante du facteur de transcription IRF 3 pour induire les IFN dans les DC humainesLYON1-BU.Sciences (692662101) / SudocSudocFranceF

Positive and Negative Selection of Human B Lymphocytes in Vitro

International audienc