Examinando por Autor "Naves, R."

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    Galectin-8 as an immunosuppressor in experimental autoimmune encephalomyelitis and a target of human early prognostic antibodies in multiple sclerosis
    (Public Library of Science, 2017-06) Pardo, E.; Cárcamo, C.; Martín, R.U.-S.; Ciampi, E.; Segovia-Miranda, F.; Curkovic-Peña, C.; Montecino, F.; Holmes, C.; Tichauer, J.E.; Acuña, E.; Osorio-Barrios, F.; Castro, M.; Cortes, P.; Oyanadel, C.; Valenzuela, D.M.; Pacheco, R.; Naves, R.; Soza, A.; González, A.
    Galectin-8 (Gal-8) is a member of a glycan-binding protein family that regulates the immune system, among other functions, and is a target of antibodies in autoimmune disorders. However, its role in multiple sclerosis (MS), an autoimmune inflammatory disease of the central nervous system (CNS), remains unknown. We study the consequences of Gal-8 silencing on lymphocyte subpopulations and the development of experimental autoimmune encephalitis (EAE), to then assess the presence and clinical meaning of anti-Gal-8 antibodies in MS patients. Lgals8/Lac-Z knock-in mice lacking Gal-8 expression have higher polarization toward Th17 cells accompanied with decreased CCR6+ and higher CXCR3+ regulatory T cells (Tregs) frequency. These conditions result in exacerbated MOG35-55 peptide-induced EAE. Gal-8 eliminates activated Th17 but not Th1 cells by apoptosis and ameliorates EAE in C57BL/6 wild-Type mice. β-gal histochemistry reflecting the activity of the Gal-8 promoter revealed Gal-8 expression in a wide range of CNS regions, including high expression in the choroid-plexus. Accordingly, we detected Gal-8 in human cerebrospinal fluid, suggesting a role in the CNS immune-surveillance circuit. In addition, we show that MS patients generate function-blocking anti-Gal-8 antibodies with pathogenic potential. Such antibodies block cell adhesion and Gal-8-induced Th17 apoptosis. Furthermore, circulating anti-Gal-8 antibodies associate with relapsing-remitting MS (RRMS), and not with progressive MS phenotypes, predicting clinical disability at diagnosis within the first year of follow-up. Our results reveal that Gal-8 has an immunosuppressive protective role against autoimmune CNS inflammation, modulating the balance of Th17 and Th1 polarization and their respective Tregs. Such a role can be counteracted during RRMS by anti-Gal-8 antibodies, worsening disease prognosis. Even though anti-Gal-8 antibodies are not specific for MS, our results suggest that they could be a potential early severity biomarker in RRMS.
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    Lymphoid B cells induce NF-κB activation in high endothelial cells from human tonsils
    (Oxford University Press [University Publisher] Japanese Society for Immunology [Associate Organisation], 2006-02) Naves, R.; Reyes, L.; Rosemblatt, M.; Jacobelli, S.; Gonzalez, A.; Bono, M.
    Immune surveillance depends on still poorly understood lymphocyte-endothelium interactions required for lymphocyte transendothelial migration into secondary lymphoid organs. The nuclear factor κB (NF-κB) regulatory system and its inhibitory IκB proteins control the inducible expression of adhesion molecules, cytokines and chemokines involved in endothelial activation and lymphocyte transmigration. Here we present results showing the activation of this system in response to the interaction of high endothelial cells from human tonsils (HUTEC) with human B and T lymphoid cell lines and primary tonsillar lymphocytes. Western blot and electrophoretic mobility shift assays show that adhesion of different lymphoid cells induce varying levels of NF-κB activation in HUTEC, with Daudi cells, tonsil-derived B cell line 10 (TBCL-10) and primary tonsillar B lymphocytes causing the strongest activation. The main NF-κB protein complexes translocated to the nucleus were p65/p50 and p50/p50. Results from reverse transcription-PCR and flow cytometry analysis of HUTEC indicate that the interaction with Daudi cells induce an increased expression of IL-6 and IL-8 mRNA and cell-surface expression of intercellular adhesion molecule-1, all of which were prevented by sodium salicylate, an inhibitor of NF-κB activation. Transwell experiments show that NF-κB activation and the response of HUTEC to the interaction of Daudi cells does not depend on direct cell-cell contact but rather on the production of soluble factors that require the presence of both cell types. These results suggest that lymphocytes and high endothelium establish a cross talk leading to NF-κB-mediated expression of cytokines and adhesion molecules, inducing endothelial cell activation.
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    Optical and near-infrared observations of SN 2011dh-The first 100 days
    (EDP Sciences, 2014-02) Ergon, M.; Sollerman, J.; Fraser, M.; Pastorello, A.; Taubenberger, S.; Elias-Rosa, N.; Bersten, M.; Jerkstrand, A.; Benetti, S.; Botticella, M.T.; Fransson, C.; Harutyunyan, A.; Kotak, R.; Smartt, S.; Valenti, S.; Bufano, F.; Cappellaro, E.; Fiaschi, M.; Howell, A.; Kankare, E.; Magill, L.; Mattila, S.; Maund, J.; Naves, R.; Ochner, P.; Ruiz, J.; Smith, K.; Tomasella, L.; Turatto, M.
    We present optical and near-infrared (NIR) photometry and spectroscopy of the Type IIb supernova (SN) 2011dh for the first 100 days. We complement our extensive dataset with Swift ultra-violet (UV) and Spitzer mid-infrared (MIR) data to build a UV to MIR bolo metric lightcurve using both photometric and spectroscopic data. Hydrodynamical modelling of the SN based on this bolometric lightcurve have been presented in Bersten et al. (2012, ApJ, 757, 31). We find that the absorption minimum for the hydrogen lines is never seen below ∼11 000 km s−1 but approaches this value as the lines get weaker. This suggests that the interface between the helium core and hydrogen rich envelope is located near this velocity in agreement with the Bersten et al. (2012) He4R270 ejecta model. Spectral modelling of the hydrogen lines using this ejecta model supports the conclusion and we find a hydrogen mass of 0.01–0.04 M to be consistent with the observed spectral evolution. We estimate that the photosphere reaches the helium core at 5–7 days whereas the helium lines appear between ∼10 and ∼15 days, close to the photosphere and then move outward in velocity until ∼40 days. This suggests that increasing non-thermal excitation due to decreasing optical depth for the γ-rays is driving the early evo lution of these lines. The Spitzer 4.5 µm band shows a significant flux excess, which we attribute to CO fundamental band emission or a thermal dust echo although further work using late time data is needed. The distance and in particular the extinction, where we use spectral modelling to put further constraints, is discussed in some detail as well as the sensitivity of the hydrodynamical modelling to errors in these quantities. We also provide and discuss pre- and post-explosion observations of the SN site which shows a reduction by ∼75 percent in flux at the position of the yellow supergiant coincident with SN 2011dh. The B, V and r band decline rates of 0.0073, 0.0090 and 0.0053 mag day−1 respectively are consistent with the remaining flux being emitted by the SN. Hence we find that the star was indeed the progenitor of SN 2011dh as previously suggested by Maund et al. (2011, ApJ, 739, L37) and which is also consistent with the results from the hydrodynamical modelling.