ADAM17-Mediated Processing of TNF-α Expressed by Antiviral Effector CD8+ T Cells Is Required for Severe T-Cell-Mediated Lung Injury

Influenza infection in humans evokes a potent CD8+ T-cell response, which is important for clearance of the virus but may also exacerbate pulmonary pathology. We have previously shown in mice that CD8+ T-cell expression of TNF-a is required for severe and lethal lung injury following recognition of an influenza antigen expressed by alveolar epithelial cells. Since TNF-a is first expressed as a transmembrane protein that is then proteolytically processed to release a soluble form, we sought to characterize the role of TNF-a processing in CD8+ T-cell-mediated injury. In this study we observed that inhibition of ADAM17-mediated processing of TNF-a by CD8+ T cells significantly attenuated the diffuse alveolar damage that occurs after T-cell transfer, resulting in enhanced survival. This was due in part to diminished chemokine expression, as TNF-aprocessing was required for lung epithelial cell expression of CXCL2 and the subsequent inflammatory infiltration. We confirmed the importance of CXCL2 expression in acute lung injury by transferring influenza-specific CD8+ T cells into transgenic mice lacking CXCR2. These mice exhibited reduced airway infiltration, attenuated lung injury, and enhanced survival. Theses studies describe a critical role for TNF-a processing by CD8+ T cells in the initiation and severity of acute lung injury, which may have important implications for limiting immunopathology during influenza infection and other human infectious or inflammatory diseases

Armement et romanisation sur le site de Gondole (Puy de Dôme)

International audienc

Chapitre 3. Le mobilier céramique

3.1. Quantification et mode de déposition du mobilier La valeur élevée du nombre de fragments collectés (218 662 restes pour 1 935 kg) témoigne d’un bon état de préservation des niveaux archéologiques et, a contrario, d’une fragmentation importante du mobilier céramique. Les éclats (moins d’1 cm2) et les tessons de petite taille (moins de 10 cm2) sont les plus nombreux (fig. 83). Les tessons de taille moyenne (de 10 à 50 cm2) sont moins fréquents et les gros fragments (taille supérieure à 50 ..

Recherches aux abords de l’<i>oppidum</i> de Gondole (Le Cendre, Puy-de-Dôme) : bilan des opérations préventives et programmées conduites depuis 2002

National audienc

Phagocyte-myocyte interactions and consequences during hypoxic wound healing

Myocardial infarction (MI), secondary to atherosclerotic plaque rupture and occlusive thrombi, triggers acute margination of inflammatory neutrophils and monocyte phagocyte subsets to the damaged heart, the latter of which may give rise briefly to differentiated macrophage-like or dendritic-like cells. Within the injured myocardium, a primary function of these phagocytic cells is to remove damaged extracellular matrix, necrotic and apoptotic cardiac cells, as well as immune cells that turn over. Recognition of dying cellular targets by phagocytes triggers intracellular signaling, particularly in macrophages, wherein cytokines and lipid mediators are generated to promote inflammation resolution, fibrotic scarring, angiogenesis, and compensatory organ remodeling. These actions cooperate in an effort to preserve myocardial contractility and prevent heart failure. Immune cell function is modulated by local tissue factors that include secreted protease activity, oxidative stress during clinical reperfusion, and hypoxia. Importantly, experimental evidence suggests that monocyte function and phagocytosis efficiency is compromised in the setting of MI risk factors, including hyperlipidemia and ageing, however underlying mechanisms remain unclear. Herein we review seminal phagocyte and cardiac molecular factors that lead to, and culminate in, the recognition and removal of dying injured myocardium, the effects of hypoxia, and their relationship to cardiac infarct size and heart healing

ADAM17 expression on transferred CD8⁺ T cells is required for enhanced airway inflammation.

<p>SPC-HA transgenic mice received 10⁷ WT or ADAM17^−/− HA-specific CD8⁺ T cells via tail vein injection. Twenty-four hours after T-cell transfer, cell-free BAL fluid was prepared and the levels of (A) CXCL2, (B) CCL2, (C) IP-10, (D) CCL11, (E) CXCL5, and (F) G-CSF were determined by Luminex assay. Data represent mean ± standard deviation. Data are representative of two mice from two independent experiments with a total of 4 mice per group. *<i>P</i><0.05, **<i>P</i><0.01.</p

Nouvelles observations sur l'occupation laténienne (II^e s. av. J-C.) et gallo-romaine (I^er-II^e s. ap. J-C.) de Bas-en-Basset (Haute-Loire), Le Maray II: Rapport de fouille archéologique 2015

International audienceL’identification des « agglomérations ouvertes » de la fin de l’âge du Fer (IIIe-Ier s. av. J.-C.) au sein de l’actuelle Auvergne, dont les limites recouvrent celles des territoires gaulois des Arvernes (Puy-de-Dôme, Cantal, Allier), des Vellaves (Haute-Loire) et des Ambluarètes (Allier), est relativement récente. Les premières hypothèses formulées en ce sens ont d’abord concerné le bassin de Clermont-Ferrand avec la mise en évidence, vers 1980, d’une première grande agglomération, connue dans la littérature archéologique sous le nom de site « d’Aulnat », quelques kilomètres à l’est de la métropole clermontoise. Dans le courant de la décennie suivante, un second site est localisé à une trentaine de kilomètres plus au nord, à l’emplacement de l’actuelle localité d’Aigueperse. Depuis, le dossier s’est considérablement enrichi et une dizaine d’agglomérations gauloises non fortifiées sont aujourd’hui identifiées de façon plus ou moins assurée en Auvergne : Les Martres-de-Veyre, Saint-Flour, Saint-Paulien, Brioude, Bas-en-Basset ; auxquelles peuvent s’ajouter, bien que moins certaines, La Roche Blanche, Lezoux et Ambert. Bien que la connaissance de ces sites soit encore souvent très largement lacunaire, les fouilles réalisées sur certains d’entre eux permettent d’en préciser les caractéristiques (chronologie, taille, la structuration interne...)

CD8⁺ T-cell-mediated acute lung injury depends in part on CXCR2 signaling.

<p>WT and CXCR2^−/− SPC-HA transgenic mice received 5×10⁶ WT HA-specific CD8⁺ T cells via tail vein injection. (A) Survival of mice after T-cell transfer was monitored daily and a striking difference in survival (<i>P</i><0.001) was observed. Representative H&E stained lung sections from (B) WT-HA or (C) CXCR2^−/−-HA mice harvested 5 days after transfer of WT HA-specific CD8⁺ T cells shown at 10x magnification with 40x inset. Data are representative of at least two independent experiments with 4-5 mice per group.</p