IL-28A (IFN-λ2) modulates lung DC function to promote Th1 immune skewing and suppress allergic airway disease.

IL-28 (IFN-λ) cytokines exhibit potent antiviral and antitumor function but their full spectrum of activities remains largely unknown. Recently, IL-28 cytokine family members were found to be profoundly down-regulated in allergic asthma. We now reveal a novel role of IL-28 cytokines in inducing type 1 immunity and protection from allergic airway disease. Treatment of wild-type mice with recombinant or adenovirally expressed IL-28A ameliorated allergic airway disease, suppressed Th2 and Th17 responses and induced IFN-γ. Moreover, abrogation of endogenous IL-28 cytokine function in IL-28Rα(-/-) mice exacerbated allergic airway inflammation by augmenting Th2 and Th17 responses, and IgE levels. Central to IL-28A immunoregulatory activity was its capacity to modulate lung CD11c(+) dendritic cell (DC) function to down-regulate OX40L, up-regulate IL-12p70 and promote Th1 differentiation. Consistently, IL-28A-mediated protection was absent in IFN-γ(-/-) mice or after IL-12 neutralization and could be adoptively transferred by IL-28A-treated CD11c(+) cells. These data demonstrate a critical role of IL-28 cytokines in controlling T cell responses in vivo through the modulation of lung CD11c(+) DC function in experimental allergic asthma. →See accompanying Closeup by Michael R Edwards and Sebastian L Johnston http://dx.doi.org/10.1002/emmm.201100143.

Selective accumulation of mature DC-Lamp+ dendritic cells in tumor sites is associated with efficient T-cell-mediated antitumor response and control of metastatic dissemination in melanoma.

The clinical relevance of dendritic cells (DCs) at the tumor site remains a matter of debate concerning their role in the generation of effective antitumor immunity in human cancers. We performed a comprehensive immunohistochemical analysis using a panel of DC-specific antibodies on regressing tumor lesions and sentinel lymph nodes (SLNs) in melanoma patients. Here we show in a case report involving spontaneous regression of metastatic melanoma that the accumulation of DC-Lamp+ DCs, clustered with tumor cells and lymphocytes, is associated with local expansion of antigen-specific memory effector CTLs. These findings were extended in a series of 19 melanoma-positive SLNs and demonstrated a significant correlation between the density of DC-Lamp+ DC infiltrates in SLNs with the absence of metastasis in downstream lymph nodes. This study, albeit performed in a limited series of patients, points to a pivotal role of mature DCs in the local expansion of efficient antitumor T-cell-mediated immune responses at the initial sites of metastasis and may have important implications regarding the prognosis, staging, and immunotherapy of melanoma patients.

Reliure de : Georgii Agricolae de Re metallica libri XII, quibus officia, instrumenta, machinae ac omnia... ad metallicam spectantia non modo... describuntur, sed et per effigies... ob oculos ponuntur... Ejusdem de animantibus subterraneis liber...

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Comprend : Marci Tullii Ciceronis vita...

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Reliure de : Bap. Platinae,... de Vitis ac gestis summorum pontificum ad sua usque tempora liber unus [cum authoris vita ex libro J. Trittemii "de Scriptoribus ecclesiasticis"]. Huic additae sunt vitae ac res gestae eorum qui interim fuere pontificum, a Paulo videlicet II, ad Julium hujus nominis III. Ejusdem item Platinae, de Falso et vero bono dialogi tres ; Contra amores I ; de Vera nobilitate I ; de Optimo cive II ; Panegyricus in Bessarionem,... Oratio ad Paulum II,... de bello Turcis inferendo. [-Panegyrici in Bap. Platinae parentalia.]

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Reliure de : Notitia utraque cum Orientis tum Occidentis ultra Arcadii Honoriique Caesarum tempora... Praecedit autem D. Andreae Alciati libellus De magistratib. civilibusque ac militaribus officiis... Cui succedit descriptio urbis Romae quae sub titulo Pub. Victoris circumfertur, et altera urbis Constantinopolitanae incerto auctore, nunquam antequam typis excusa... Subjungitur Notitiis vetustus liber de rebus bellicis ad Theodosium Aug. et filios ejus Arcadium atque Honorium, ut videtur, scriptus, incerto autore. Item... Disputatio Adriani Aug. et Epicteti philosophi

[Notitia dignitatum omnium tam civilium quam militarium (latin). 1552]

Reliure de : Andreae Vesalii,... Epistola [ad Joachimum Roelants], rationem modumque propinandi radicis Chynae decocti, quo nuper... Carolus V. imperator usus est, pertractans ; et praeter alia quaedam, epistolae cujusdam ad Jacobum Sylvium sententiam recensens, veritatis ac potissimum humanae fabricae studiosis perutilem ; quum qui hactenus in illa nimium Galeno creditum sit, facile commonstret. Accessit quoque locuples rerum et verborum in hac ipsa epistola memorabilium index... [A Francisco Vesalio, auctoris fratre, editum.]

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[Illustrations de Brevis ac dilucida Burgundiae superioris... item brevis ad modum totius Galliae descriptio per eudem] / [Non identifié] ; Gilbert Cousin, aut. du texte

Comprend : [Planche entre les p. 48-49. Deux planches. Représentation du côté ouest et du côté est d'une ville. Habitations burgondes.] [Cote : BNF C214317] ; [Planche dépliante entre les p. 48-49. Partie gauche de la planche représentant le côté est d'une ville. Habitations burgondes.] [Cote : BNF C94455]

[Illustrations de Orbis situ ac descriptione...] / [Non identifié] ; Le Père Franciscus Monachus, aut. du texte

Comprend : [ Folios A1v ° et A2r °. Vue des deux cartes en couleur de l'hémisphère Européen-Africain et de l'hémisphère Américain. XVIè siècle.] [ Cote : BNF RCB 8010. ]

Human alveolar macrophages infected by virulent bacteria expressing SipB are a major source of active interleukin-18.

Recent publications have demonstrated that the protease caspase-1 is responsible for the processing of pro-interleukin 18 (IL-18) into the active form. Studies on cell lines and murine macrophages have shown that the bacterial invasion factor SipB activates caspase-1, triggering cell death. Thus, we investigated the role of SipB in the activation and release of IL-18 in human alveolar macrophages (AM), which are the first line of defense against inhaled pathogens. Under steady-state conditions, AM are a more important source of IL-18 than are dendritic cells (DC) and monocytes. Cytokine production by AM and DC was compared after both types of cells had been infected with a virulent strain of Salmonella enterica serovar Typhimurium and an isogenic sipB mutant, which were used as an infection model. Infection with virulent Salmonella led to marked cell death with features of apoptosis while both intracellular activation and release of IL-18 were demonstrated. In contrast, the sipB mutant did not induce such cell death or the release of active IL-18. The specific caspase-1 inhibitor Ac-YVAD-CMK blocked the early IL-18 release in AM infected with the virulent strain. However, the type of Salmonella infection did not differentially regulate IL-18 gene expression. We concluded that the bacterial virulence factor SipB plays an essential posttranslational role in the intracellular activation of IL-18 and the release of the cytokine in human AM.