B cell activating factor is central to bleomycin- and IL-17-mediated experimental pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive devastating, yet untreatable fibrotic disease of unknown origin. We investigated the contribution of the B-cell activating factor (BAFF), a TNF family member recently implicated in the regulation of pathogenic IL-17-producing cells in autoimmune diseases. The contribution of BAFF was assessed in a murine model of lung fibrosis induced by airway administered bleomycin. We show that murine BAFF levels were strongly increased in the bronchoalveolar space and lungs after bleomycin exposure. We identified Gr1(+) neutrophils as an important source of BAFF upon BLM-induced lung inflammation and fibrosis. Genetic ablation of BAFF or BAFF neutralization by a soluble receptor significantly attenuated pulmonary fibrosis and IL-1β levels. We further demonstrate that bleomycin-induced BAFF expression and lung fibrosis were IL-1β and IL-17A dependent. BAFF was required for rIL-17A-induced lung fibrosis and augmented IL-17A production by CD3(+) T cells from murine fibrotic lungs ex vivo. Finally we report elevated levels of BAFF in bronchoalveolar lavages from IPF patients. Our data therefore support a role for BAFF in the establishment of pulmonary fibrosis and a crosstalk between IL-1β, BAFF and IL-17A.

Il luogo delle Muse: saggi di letteratura contemporanea

Serie di saggi dedicati alla poesia italiana del Novecento, muovendo da un'analisi della poetica dell'"ultimo" Montale, caratterizzata da un ambito più prosastico e satirico e da una ricerca di nuovi significati da attribuire alla poesia stessa. Lo studio di alcuni dei più importanti rappresentanti della letteratura poetica del secondo Novecento prosegue nella seconda sezione, dedicata a Giorgio Orelli, considerato uno dei maggiori poeti viventi in lingua italiana, a Remo Fasani, a Cristina Campo, a Giancarlo Majorino, e, infine, a Gilberto Isella, la cui ricerca poetica si inserisce a pieno titolo nella grande stagione del simbolismo europeo. La terza sezione è dedicata interamente a Guido Ceronetti, poeta, scrittore, traduttore (sia dal latino, sia dall'antico ebraico) e autore di teatro. Conclude il volume uno studio panoramico sugli scrittori della Svizzera italiana: si tratta di esperienze che hanno in comune una straordinaria capacità di reinterpretare la tradizione letteraria italiana, fino ad aprirla verso orizzonti non solo transnazionali, ma anche inediti ed innovativi.

Le vaccin contre le Zona : que faut-il en penser ? [Herpes zoster vaccine: What do we have to think about?]

Depuis 2007, le vaccin vivant atténué contre le zona dispose d'une autorisation de mise sur le marché au niveau européen. Fin 2015-début 2016, il devrait enfin être disponible en France. Cet article répond à vos interrogations concernant son intérêt, son efficacité, sa tolérance et ses bénéfices pour la société, dans la prévention du zona et d'une de ses complications les plus fréquentes et la plus invalidante : les douleurs post-zostériennes.

“L’Emozione di conoscere e il desiderio di esistere”: Què és i com afecta la seva pràctica en el desenvolupament de l'autonomia de l'infant

El treball que es presenta a continuació pretén fer un aprofundiment en la metodologia pedagògica “Emozione di conoscere e desiderio di esistere”, nascuda a Itàlia i usada com a referent en l’Educació Especial, amb la intensió de poder valorar de quina manera afecta la seva pràctica en el desenvolupament de l’autonomia de l’infant. Per fer-ho, s’ha fet un recull dels estudis més rellevants relacionats amb el mètode “Emozione di conocscere” i amb el concepte d’autonomia. Seguidament, s’ha fet una observació acurada per poder descriure la posada en pràctica d’un projecte basat en aquesta metodologia i analitzar com aquest intervé en desenvolupar dita competència en els alumnes. Tot això, emmarcat dins l’escenari de la “Scuola Elementare Pirazzini”, situada al centre – nord d’Itàlia.

Nitric oxide sustains IL-1β expression in human dendritic cells enhancing their capacity to induce IL-17-producing T-cells.

The role played by lung dendritic cells (DCs) which are influenced by external antigens and by their redox state in controlling inflammation is unclear. We studied the role played by nitric oxide (NO) in DC maturation and function. Human DCs were stimulated with a long-acting NO donor, DPTA NONOate, prior to exposure to lipopolysaccharide (LPS). Dose-and time-dependent experiments were performed with DCs with the aim of measuring the release and gene expression of inflammatory cytokines capable of modifying T-cell differentiation, towardsTh1, Th2 and Th17 cells. NO changed the pattern of cytokine release by LPS-matured DCs, dependent on the concentration of NO, as well as on the timing of its addition to the cells during maturation. Addition of NO before LPS-induced maturation strongly inhibited the release of IL-12, while increasing the expression and release of IL-23, IL-1β and IL-6, which are all involved in Th17 polarization. Indeed, DCs treated with NO efficiently induced the release of IL-17 by T-cells through IL-1β. Our work highlights the important role that NO may play in sustaining inflammation during an infection through the preferential differentiation of the Th17 lineage.

How to get rid of a pathobiontic bacterium from the stomach mucosa : role of inflammatory monocytes and IL-22 in the vaccine-induced reduction of helicobacter infection

Helicobacter pylori is a bacterium colonizing the human stomach. To prevent or cure this potentially detrimental infection, vaccination might be a suitable alternative to antibiotic therapies. Recently, a study has demonstrated that a vaccine efficiently prevented H pylori infection in human. However, the mechanisms leading to protection remain elusive. In mice, the vaccine-induced protective response relies on CD4+ T cells and especially on Thl7 response. Nevertheless, the factors mediating the reduction of H pylori infection are not fully characterized. Hence, the aim of my thesis was to characterize the factors associated with the Thl7 response. In the context of the vaccine-induced reduction of Helicobacter infection, I first focused on the role of inflammatory monocytes. I showed that CDllb+Ly6CLOW inflammatory monocytes accumulated in the stomach of vaccinated mice in association with the reduction of Helicobacter infection. Remarkably, the depletion of inflammatory monocytes delayed the vaccine-induced protective response. Concerning the role of these cells, I demonstrated that inflammatory monocytes extracted from the stomach of vaccinated mice produced iNOS and killed H pylori in vitro. In a next step, I evaluated the role of IL-22 during the vaccine-induced response. IL-22, which is linked to the Thl7 response, increases innate defense mechanisms of epithelial cells. I demonstrated that IL-22 produced by antigen- specific Thl7 was increased in the stomach of vaccinated mice during the protective response. Interestingly, neutralization of IL-22 was associated with an impaired vaccine-induced protective response. Then, I demonstrated that IL-22 induced antimicrobial peptides (AMPs) secretion by epithelial cells. These AMPs killed H pylori in vitro. In conclusion, I showed that both inflammatory monocytes and IL-22 participated to the vaccine induced reduction of Helicobacter infection. In addition, I demonstrated that the epithelium along with inflammation induced by Thl7 response is a critical factor mediating reduction of Helicobacter infection.