Abstract:
:Changes in the epigenetic landscape of immune cells are a crucial component of gene activation during the induction of inflammatory responses, therefore it has been hypothesized that epigenetic modulation could be employed to restore homeostasis in inflammatory scenarios. Fungal pathogens cause a large burden of morbidity and even mortality due to the hyperinflammatory processes that induce mucosal, allergic or systemic infections. Bromodomain and extraterminal domain (BET) proteins are considered as one as the most tantalizing pharmacological targets for the modulation of inflammatory responses at the epigenetic level. Nothing is known of the role of BET inhibitors on the inflammation induced by fungal pathogens. In the present study, we assessed the in vitro efficacy of the small molecular histone mimic BET inhibitor I-BET151 to modulate innate immune responses during fungal-immune interaction with the clinically relevant fungal pathogens Candida albicans and Aspergillus fumigatus. Our results prove that BET inhibitors (I-BETs) represent an important modulator of inflammation induced by fungal pathogens: both direct production of proinflammatory cytokines and the induction of trained immunity were inhibited by I-BET151. These modulatory effects are likely to have important potential implications in clinically relevant situations.
journal_name
Eur J Immunoljournal_title
European journal of immunologyauthors
Domínguez-Andrés J,Ferreira AV,Jansen T,Smithers N,Prinjha RK,Furze RC,Netea MGdoi
10.1002/eji.201848081subject
Has Abstractpub_date
2019-11-01 00:00:00pages
2044-2050issue
11eissn
0014-2980issn
1521-4141journal_volume
49pub_type
杂志文章abstract::Abnormal cytokine production can contribute in many instances to the development of pathology. Our study focuses on the regulation of interleukin (IL)-6 production in vitro in brain-specific endothelial cells (BEC) under physiological conditions and in a model of human T leukemia virus-1 (HTLV-1) infection. IL-6 produ...
journal_title:European journal of immunology
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journal_title:European journal of immunology
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doi:10.1002/eji.1830270413
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journal_title:European journal of immunology
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abstract::Inflammatory bowel disease (IBD) is characterized by a dysregulated intestinal immune response with elevated levels of the Th1 cytokines TNF, IL-12 and IFN-gamma. The luminal flora has been implicated as a major factor contributing to the initiation and perpetuation of chronic intestinal inflammation by as yet unknown...
journal_title:European journal of immunology
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abstract::Primary proliferative T cell responses require stimulation with antigen-pulsed dendritic cells (Ag-DC). Here we show that for optimal stimulation, dendritic cells (DC) not exposed directly to antigen are also required. Ag-DC added to DC-depleted T cells caused negligible primary stimulation; adding back DC resulted in...
journal_title:European journal of immunology
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doi:10.1002/(SICI)1521-4141(199805)28:05<1636::AID-IMM
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abstract::In this study we have examined the role of small numbers of adherent cells in the stimulation of highly purified resting T lymphocytes by cross-linked monoclonal anti-CD3 antibodies (T3). T cells were obtained by 3 cycles of purification, using adherence to plastic surface, nylon wool column separation and rosetting w...
journal_title:European journal of immunology
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doi:10.1002/eji.1830171122
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abstract::Membrane-bound immunoglobulins of the IgM and IgD class are expressed on the B cell surface in association with a disulfide-linked heterodimer consisting of alpha and beta subunits. While the alpha component of the IgM antigen receptor (IgM-alpha, 34 kDa) is encoded by the B cell-specific gene mb-1, the gene coding fo...
journal_title:European journal of immunology
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doi:10.1002/eji.1830211012
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abstract::In a search for proteins involved in signal transduction through the T cell receptor (TcR/CD3 complex), a recently developed highly efficient method for labeling of nucleotide binding proteins in permeabilized cells was applied. Here, we report that human CD3-gamma could be labeled by periodate-oxidized [alpha-32P] GT...
journal_title:European journal of immunology
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doi:10.1002/eji.1830230224
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journal_title:European journal of immunology
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doi:10.1002/eji.1830250907
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journal_title:European journal of immunology
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doi:10.1002/eji.200526116
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abstract::The biochemical behavior and peptide binding properties of a soluble form of the human class II DR4Dw4 molecule (PI-DR4Dw4) were compared to DR4Dw4 molecules containing the transmembrane and cytoplasmic domains that were purified both from B and transfected chinese hamster ovary cells. Recombinant and B cell-derived D...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830230112
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abstract::In this study, we demonstrated that antibodies reactive with a common beta 1 subunit (CD29) of the VLA family of antigens could synergize with CD3 but not CD2 in inducing CD4 cell proliferation in a serum-free culture system. The extent of activation was similar to that obtained when CD4 cells were cultured with anti-...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830210212
更新日期:1991-02-01 00:00:00
abstract::The TCR structure of T cell hybridomas recognizing a tumor glycan-defined epitope has been studied using reverse transcriptase-PCR and gene sequencing. The hybridomas had been raised against a glycopeptide, T72(Tn), consisting of the mouse hemoglobin-derived decapeptide Hb(67 - 76), O-glycoslated in position 72 with a...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/(SICI)1521-4141(199909)29:09<2759::AID-IMM
更新日期:1999-09-01 00:00:00
abstract::APO-1/Fas (CD95) is a transmembrane receptor that transduces apoptotic signals within various cells including T and B cells. The APO-1 gene was found to be defective in lpr mice. In these mice insertion of a retrotransposon gives rise to transcription of an abnormal mRNA and only a fraction of wild-type APO-1 mRNA. It...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830241231
更新日期:1994-12-01 00:00:00
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journal_title:European journal of immunology
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doi:10.1002/eji.200526154
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830240738
更新日期:1994-07-01 00:00:00
abstract::Tissue factor (TF) is a transmembrane glycoprotein that plays an essential role in hemostasis by activating coagulation. TF is also expressed by monocytes/macrophages as part of the innate immune response to infections. In the current study, we determined the role of TF expressed by myeloid cells during Mycobacterium ...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.201545817
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journal_title:European journal of immunology
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doi:10.1002/eji.1830220419
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journal_title:European journal of immunology
pub_type: 杂志文章
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journal_title:European journal of immunology
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830220324
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830260918
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830170906
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abstract::Studies of chronic viral infections have highlighted the phenotypic and functional heterogeneity of antigen-specific T cells and suggested that polyfunctional T cells that secrete multiple cytokines and are able to proliferate on encounter with antigen are more likely than single cytokine secretors to represent correl...
journal_title:European journal of immunology
pub_type: 评论,杂志文章
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更新日期:2010-08-01 00:00:00
abstract::Humanized BALB/c mice (termed trimera mice) conditioned by lethal total body irradiation and bone marrow transplantation from SCID mice have been described to support rapid engraftment of human peripheral blood mononuclear cells (PBMC) and the induction of strong B and T cell responses after immunization in vivo. More...
journal_title:European journal of immunology
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abstract::A considerable fraction of T cells express two distinct T cell receptors (TCR), mainly due to expression of two TCR alpha chains. It has been suggested that such dual-TCR cells could have a role in autoimmunity. However, as such cells express less of each TCR, they could be less sensitive to their physiological ligand...
journal_title:European journal of immunology
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journal_title:European journal of immunology
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doi:10.1002/eji.1830060908
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abstract::Respiratory syncytial virus (RSV) causes severe bronchiolitis in infants worldwide. The immunological factors responsible for RSV susceptibility in infants are poorly understood. Here, we used the BALB/c mouse model of neonatal RSV infection to study the mechanisms leading to severe disease upon reexposure to the viru...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.201545929
更新日期:2016-04-01 00:00:00
abstract::Endoglin is an homodimeric membrane antigen with capacity to bind transforming growth factor-beta (TGF-beta) and whose expression is up-regulated on myeloid cells upon differentiation to macrophages. We have isolated full-length cDNA clones from a lambda gt 10 library, prepared from phorbol 12-myristate 13-acetate-dif...
journal_title:European journal of immunology
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doi:10.1002/eji.1830230943
更新日期:1993-09-01 00:00:00