59 research outputs found

    Selective APRIL Blockade Delays Systemic Lupus Erythematosus in Mouse

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    SLE pathogenesis is complex, but it is now widely accepted that autoantibodies play a key role in the process by forming excessive immune complexes; their deposits within tissues leading to inflammation and functional damages. A proliferation inducing ligand (APRIL) is a member of the tumor necrosis factor (TNF) superfamily mediating antibody-producing plasma cell (PC)-survival that may be involved in the duration of pathogenic autoantibodies in lupus. We found significant increases of APRIL at the mRNA and protein levels in bone marrow but not spleen cells from NZB/W lupus mice, as compared to control mice. Selective antibody-mediated APRIL blockade delays disease development in this model by preventing proteinuria, kidney lesions, and mortality. Notably, this was achieved by decreasing anti-DNA and anti-chromatin autoantibody levels, without any perturbation of B- and T- cell homeostasis. Thus, anti-APRIL treatment may constitute an alternative therapy in SLE highly specific to PCs compared to other B-cell targeting therapies tested in this disease, and likely to be associated with less adverse effects than any anti-inflammatory and immunosuppressant agents previously used

    Notes for genera: basal clades of Fungi (including Aphelidiomycota, Basidiobolomycota, Blastocladiomycota, Calcarisporiellomycota, Caulochytriomycota, Chytridiomycota, Entomophthoromycota, Glomeromycota, Kickxellomycota, Monoblepharomycota, Mortierellomycota, Mucoromycota, Neocallimastigomycota, Olpidiomycota, Rozellomycota and Zoopagomycota)

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    Compared to the higher fungi (Dikarya), taxonomic and evolutionary studies on the basal clades of fungi are fewer in number. Thus, the generic boundaries and higher ranks in the basal clades of fungi are poorly known. Recent DNA based taxonomic studies have provided reliable and accurate information. It is therefore necessary to compile all available information since basal clades genera lack updated checklists or outlines. Recently, Tedersoo et al. (MycoKeys 13:1--20, 2016) accepted Aphelidiomycota and Rozellomycota in Fungal clade. Thus, we regard both these phyla as members in Kingdom Fungi. We accept 16 phyla in basal clades viz. Aphelidiomycota, Basidiobolomycota, Blastocladiomycota, Calcarisporiellomycota, Caulochytriomycota, Chytridiomycota, Entomophthoromycota, Glomeromycota, Kickxellomycota, Monoblepharomycota, Mortierellomycota, Mucoromycota, Neocallimastigomycota, Olpidiomycota, Rozellomycota and Zoopagomycota. Thus, 611 genera in 153 families, 43 orders and 18 classes are provided with details of classification, synonyms, life modes, distribution, recent literature and genomic data. Moreover, Catenariaceae Couch is proposed to be conserved, Cladochytriales Mozl.-Standr. is emended and the family Nephridiophagaceae is introduced

    In situ detection of APRIL-rich niches for plasma-cell survival and their contribution to B-cell lymphoma development

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    A proliferation inducing ligand (APRIL) is one of the most recently cloned members of the tumor necrosis factor (TNF) family. Early experiments implicated a pathophysiological role for APRIL in the promotion of solid tumors. Later, identification of APRIL receptors on B lymphocytes indicated a physiological role for APRIL in humoral responses. We have been able to generate antibodies that detect APRIL protein in human tissues. The study of in situ APRIL expression showed that APRIL mainly regulates late stages of B-cell humoral responses. It also provided evidence that APRIL may modulate tumor development in patients, but only for specific B-cell malignancies. Here, we will review to what extent fine characterization of in situ expression adds valuable information on APRIL (patho) physiological functions

    Functional Status of Mitochondrial Pore in the Brain of Laboratory Rats Subjected to Prolonged Emotional Stress

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    We have studied the functional status of the mitochondrial membrane pore in the brain of laboratory rats under the stress caused by 30-day isolation and violation of diurnal cycles. It has been established that the functional status of the MMTP changes under the stress. Particularly, the MPTP is activated as the pore opens affected by an increased concentration of cytoplasmic Са2+ and reduced content of mitochondrial Са2+. It has been suggested that the Са2+-induced opening of the pore is a result of the intensified oxidative processes in the brain, as a result of energy deficiency and a reduced activity of anti-oxidative enzymes

    In situ detection of APRIL-rich niches for plasma-cell survival and their contribution to B-cell lymphoma development

    No full text
    A proliferation inducing ligand (APRIL) is one of the most recently cloned members of the tumor necrosis factor (TNF) family. Early experiments implicated a pathophysiological role for APRIL in the promotion of solid tumors. Later, identification of APRIL receptors on B lymphocytes indicated a physiological role for APRIL in humoral responses. We have been able to generate antibodies that detect APRIL protein in human tissues. The study of in situ APRIL expression showed that APRIL mainly regulates late stages of B-cell humoral responses. It also provided evidence that APRIL may modulate tumor development in patients, but only for specific B-cell malignancies. Here, we will review to what extent fine characterization of in situ expression adds valuable information on APRIL (patho) physiological functions

    Homeostasis of naive and memory CD4+ T cells: IL-2 and IL-7 differentially regulate the balance between proliferation and Fas-mediated apoptosis

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    Cytokines play a crucial role in the maintenance of polyclonal naive and memory T cell populations. It has previously been shown that ex vivo, the IL-7 cytokine induces the proliferation of naive recent thymic emigrants (RTE) isolated from umbilical cord blood but not mature adult-derived naive and memory human CD4(+) T cells. We find that the combination of IL-2 and IL-7 strongly promotes the proliferation of RTE, whereas adult CD4(+) T cells remain relatively unresponsive. Immunological activity is controlled by a balance between proliferation and apoptotic cell death. However, the relative contributions of IL-2 and IL-7 in regulating these processes in the absence of MHC/peptide signals are not known. Following exposure to either IL-2 or IL-7 alone, RTE, as well as mature naive and memory CD4(+) T cells, are rendered only minimally sensitive to Fas-mediated cell death. However, in the presence of the two cytokines, Fas engagement results in a high level of caspase-dependent apoptosis in both RTE as well as naive adult CD4(+) T cells. In contrast, equivalently treated memory CD4(+) T cells are significantly less sensitive to Fas-induced cell death. The increased susceptibility of RTE and naive CD4(+) T cells to Fas-induced apoptosis correlates with a significantly higher IL-2/IL-7-induced Fas expression on these T cell subsets than on memory CD4(+) T cells. Thus, IL-2 and IL-7 regulate homeostasis by modulating the equilibrium between proliferation and apoptotic cell death in RTE and mature naive and memory T cell subsets
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