Macroautophagy in lymphatic endothelial cells inhibits T cell-mediated autoimmunity.

Lymphatic endothelial cells (LECs) present peripheral tissue antigens to induce T cell tolerance. In addition, LECs are the main source of sphingosine-1-phosphate (S1P), promoting naive T cell survival and effector T cell exit from lymph nodes (LNs). Autophagy is a physiological process essential for cellular homeostasis. We investigated whether autophagy in LECs modulates T cell activation in experimental arthritis. Whereas genetic abrogation of autophagy in LECs does not alter immune homeostasis, it induces alterations of the regulatory T cell (T reg cell) population in LNs from arthritic mice, which might be linked to MHCII-mediated antigen presentation by LECs. Furthermore, inflammation-induced autophagy in LECs promotes the degradation of Sphingosine kinase 1 (SphK1), resulting in decreased S1P production. Consequently, in arthritic mice lacking autophagy in LECs, pathogenic Th17 cell migration toward LEC-derived S1P gradients and egress from LNs are enhanced, as well as infiltration of inflamed joints, resulting in exacerbated arthritis. Our results highlight the autophagy pathway as an important regulator of LEC immunomodulatory functions in inflammatory conditions

VALEUR INFORMATIVE DE LA SURVENUE D'UNE DESTRUCTION ARTICULAIRE A UN AN, DES PARAMETRES CLINIQUES, DES PARAMETRES BIOLOGIQUES D'INFLAMMATION, DE YKL-40 ET DE HLA AU COURS DE LA POLYARTHRITE RHUMATOIDE

AMIENS-BU Santé (800212102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Rôle de l'angiogénèse dans la polyarthrite rhumatoïde

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Deux fermes voisines des XVIe- début XVIIIe siècles

International audienc

Les fermes d’Herneuse à Verberie (Oise). Deux fermes voisines des XVIe-début XVIIIe siècles

Im Norden von Verberie, zwischen der Oise und dem königlichen Forst von Compiègne wurden zwei Bauernhöfe des 16. und Anfang des 18. Jh. ausgegraben. Obwohl sie geschliffen worden waren, ist die Organisation der Höfe zu erkennen, zudem können das Keramik-und Metallmobiliar (Geschirr und Werkzeuge) sowie Spuren von Viehzucht und Fleischnahrung identifiziert werden. Anhand von Urkunden aus den Archiven des Departements wurden die Hypothesen bezüglich der Natur und der Funktion der bei der Grabung erkannten Spuren bestätigt. Zudem konnten diese Höfe in ihrem geschichtlichen Umfeld erfasst werden. Sie besaßen unterschiedliche rechtliche Stellungen, bei dem einen handelte es sich um kirchlichen, bei dem anderen um weltlichen Grundbesitz. Sie waren Gegenstand von Pachtverträgen, von denen bis heute nur wenige Erwähnungen gefunden wurden. Archäologische Beispiele dieser Art sind selten. Sie veranschaulichen die neuzeitlichen Bauernhöfe des Valois aus der Periode zwischen der Krisenzeit des 15. Jh. und der Phase der Konzentration des Grundbesitzes im späten 17. Jh.Two farms in activity from the 16th to the early 18th century have been excavated north of Verberie, between the river Oise and the royal forest of Compiègne. Although levelled off, the remains have yielded information about the organization of the farms, their ceramic and metallic utensils (crockery and tools), and some evidence concerning the cattle and the consumption of meat. Limited documentary evidence from the district Archives tends to support the hypotheses concerning the nature and the function of the remains discovered in the excavations and provides the basis for a preliminary historical overview of the environment of these settlements. The two farms did not have the same status, the one being ecclesiastical and the other secular, and they were the subject of successive leases to which only a few references have so far been found in our documentary evidence. Such archaeological examples are rare ; they appear to be, on their own scale, typical of the farms in the Valois district during the Modern era, between the crisis of the 15th century and the phase of concentration of the landed property at the end of the 17th century.Deux fermes, des XVIe siècle-début XVIIIe siècle, ont été fouillées au nord de Verberie, entre l’Oise et la forêt royale de Compiègne. Bien qu’arasés, les vestiges permettent la reconnaissance de l’organisation des fermes, de leur mobilier céramique et métallique (vaisselle et outils) et des témoignages liés au bétail et à l’alimentation carnée. Quelques éléments documentaires, recueillis aux archives départementales, ont permis d’étayer les hypothèses quant à la nature et la fonction des vestiges reconnus à la fouille et d’initier un panorama historique de l’environnement de ces établissements. De statuts différents, propriété ecclésiastique pour l’une et civile pour l’autre, elles ont fait l’objet de baux successifs dont seules de rares mentions ont été pour l’heure retrouvées. Ces exemples archéologiques sont rares, ils apparaissent, à leur échelle, comme des illustrations des fermes du Valois de l’époque moderne, compris entre la période de crise du XVe siècle et la phase de concentration foncière de la fin du XVIIe siècle.Bruley-Chabot Gaëlle, Clavel Benoît, Jouanin Gaëtan, Facquez Dorothée, Legros Vincent, Bernard Jean-Louis. Les fermes d’Herneuse à Verberie (Oise). Deux fermes voisines des XVIe-début XVIIIe siècles. In: Revue archéologique de Picardie, n°3-4, 2012. pp. 207-295

Quantification of the Effects on Viral DNA Synthesis of Reverse Transcriptase Mutations Conferring Human Immunodeficiency Virus Type 1 Resistance to Nucleoside Analogues

Human immunodeficiency virus type I (HIV-1) reverse transcriptase (RT) resistance mutations reduce the susceptibility of the virus to nucleoside analogues but may also impair viral DNA synthesis. To further characterize the effect of nucleoside analogue resistance mutations on the efficiency and kinetics of HIV-1 DNA synthesis and to evaluate the impact of the depletion of deoxynucleoside triphosphates (dNTP) on this process, DNA synthesis was evaluated by allowing DNA synthesis to proceed with natural HIV-1 templates and primers, either within permeabilized viral particles or in newly infected cells, and quantifying the products by real-time PCR. Three recombinant viruses derived from three pNL4-3 molecular clones expressing mutations associated with resistance to zidovudine: a clone expressing RT mutation M184V, a clone expressing mutations M41L plus T215Y (M41L+T215Y), and clinical isolate BV34 (carrying seven resistance mutations). Following infection of P4 cells, the BV34 mutant, but not viruses expressing the M184V mutation or M41L+T215Y, exhibited a defect in DNA synthesis. Importantly, however, for mutants carrying the M184V mutation or M41L+T215Y mutations, a defect could be detected by using target cells in which dATP pools had been reduced by pretreatment with hydroxyurea. Based on these observations, we developed a recombinant-virus assay to assess the effects of hydroxyurea pretreatment on infectivity of viruses carrying plasma-derived RT sequences from patients with nucleoside resistance. Using this assay, we found that many, but not all, viruses carrying RT resistance mutations display an increased sensitivity to hydroxyurea, suggesting that the impact of RT resistance mutations on viral replication may be more profound in cell populations characterized by smaller dNTP pools