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  1. Article ; Online: Bacteriotherapy with human skin commensals in atopic dermatitis.

    Castillo-González, Raquel / Fernández-Delgado, Irene / Comberiati, Pasquale

    Allergy

    2021  Volume 77, Issue 4, Page(s) 1331–1333

    MeSH term(s) Dermatitis, Atopic/therapy ; Humans ; Microbiota ; Skin
    Language English
    Publishing date 2021-11-06
    Publishing country Denmark
    Document type News
    ZDB-ID 391933-x
    ISSN 1398-9995 ; 0105-4538
    ISSN (online) 1398-9995
    ISSN 0105-4538
    DOI 10.1111/all.15162
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    In stock of ZB MED Cologne/Königswinter

    Uh III Zs.150: Show issues Location:
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    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 125: Show issues

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  2. Article: Immune Regulation by Dendritic Cell Extracellular Vesicles in Cancer Immunotherapy and Vaccines.

    Fernández-Delgado, Irene / Calzada-Fraile, Diego / Sánchez-Madrid, Francisco

    Cancers

    2020  Volume 12, Issue 12

    Abstract: Extracellular vesicles (EVs) play a crucial role in intercellular communication as vehicles for the transport of membrane and cytosolic proteins, lipids, and nucleic acids including different RNAs. Dendritic cells (DCs)-derived EVs (DEVs), albeit ... ...

    Abstract Extracellular vesicles (EVs) play a crucial role in intercellular communication as vehicles for the transport of membrane and cytosolic proteins, lipids, and nucleic acids including different RNAs. Dendritic cells (DCs)-derived EVs (DEVs), albeit variably, express major histocompatibility complex (MHC)-peptide complexes and co-stimulatory molecules on their surface that enable the interaction with other immune cells such as CD8
    Language English
    Publishing date 2020-11-28
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers12123558
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  3. Article ; Online: MiRNA post-transcriptional modification dynamics in T cell activation.

    Rodríguez-Galán, Ana / Dosil, Sara G / Gómez, Manuel José / Fernández-Delgado, Irene / Fernández-Messina, Lola / Sánchez-Cabo, Fátima / Sánchez-Madrid, Francisco

    iScience

    2021  Volume 24, Issue 6, Page(s) 102530

    Abstract: T cell activation leads to extensive changes in the miRNA repertoire. Although overall miRNA expression decreases within a few hours of T cell activation, some individual miRNAs are specifically upregulated. Using next-generation sequencing, we assessed ... ...

    Abstract T cell activation leads to extensive changes in the miRNA repertoire. Although overall miRNA expression decreases within a few hours of T cell activation, some individual miRNAs are specifically upregulated. Using next-generation sequencing, we assessed miRNA expression and post-transcriptional modification kinetics in human primary CD4+ T cells upon T cell receptor (TCR) or type I interferon stimulation. This analysis identified differential expression of multiple miRNAs not previously linked to T cell activation. Remarkably, upregulated miRNAs showed a higher frequency of 3' adenylation. TCR stimulation was followed by increased expression of RNA modifying enzymes and the RNA degrading enzymes Dis3L2 and Eri1. In the midst of this adverse environment, 3' adenylation may serve a protective function that could be exploited to improve miRNA stability for T cell-targeted therapy.
    Language English
    Publishing date 2021-05-12
    Publishing country United States
    Document type Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2021.102530
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  4. Article ; Online: ISG20L2: an RNA nuclease regulating T cell activation.

    Rodríguez-Galán, Ana / Dosil, Sara G / Hrčková, Anna / Fernández-Messina, Lola / Feketová, Zuzana / Pokorná, Julie / Fernández-Delgado, Irene / Camafeita, Emilio / Gómez, Manuel José / Ramírez-Huesca, Marta / Gutiérrez-Vázquez, Cristina / Sánchez-Cabo, Fátima / Vázquez, Jesús / Vaňáčová, Štěpánka / Sánchez-Madrid, Francisco

    Cellular and molecular life sciences : CMLS

    2023  Volume 80, Issue 9, Page(s) 273

    Abstract: ISG20L2, a 3' to 5' exoribonuclease previously associated with ribosome biogenesis, is identified here in activated T cells as an enzyme with a preferential affinity for uridylated miRNA substrates. This enzyme is upregulated in T lymphocytes upon TCR ... ...

    Abstract ISG20L2, a 3' to 5' exoribonuclease previously associated with ribosome biogenesis, is identified here in activated T cells as an enzyme with a preferential affinity for uridylated miRNA substrates. This enzyme is upregulated in T lymphocytes upon TCR and IFN type I stimulation and appears to be involved in regulating T cell function. ISG20L2 silencing leads to an increased basal expression of CD69 and induces greater IL2 secretion. However, ISG20L2 absence impairs CD25 upregulation, CD3 synaptic accumulation and MTOC translocation towards the antigen-presenting cell during immune synapsis. Remarkably, ISG20L2 controls the expression of immunoregulatory molecules, such as AHR, NKG2D, CTLA-4, CD137, TIM-3, PD-L1 or PD-1, which show increased levels in ISG20L2 knockout T cells. The dysregulation observed in these key molecules for T cell responses support a role for this exonuclease as a novel RNA-based regulator of T cell function.
    MeSH term(s) Antigen-Presenting Cells ; Endonucleases ; Lymphocyte Activation ; MicroRNAs/genetics ; Humans
    Chemical Substances Endonucleases (EC 3.1.-) ; MicroRNAs
    Language English
    Publishing date 2023-08-30
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1358415-7
    ISSN 1420-9071 ; 1420-682X
    ISSN (online) 1420-9071
    ISSN 1420-682X
    DOI 10.1007/s00018-023-04925-2
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 195: Show issues Location:
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  5. Article ; Online: Post-translational add-ons mark the path in exosomal protein sorting.

    Moreno-Gonzalo, Olga / Fernandez-Delgado, Irene / Sanchez-Madrid, Francisco

    Cellular and molecular life sciences : CMLS

    2017  Volume 75, Issue 1, Page(s) 1–19

    Abstract: Extracellular vesicles (EVs) are released by cells to the extracellular environment to mediate inter-cellular communication. Proteins, lipids, nucleic acids and metabolites shuttled in these vesicles modulate specific functions in recipient cells. The ... ...

    Abstract Extracellular vesicles (EVs) are released by cells to the extracellular environment to mediate inter-cellular communication. Proteins, lipids, nucleic acids and metabolites shuttled in these vesicles modulate specific functions in recipient cells. The enrichment of selected sets of proteins in EVs compared with global cellular levels suggests the existence of specific sorting mechanisms to specify EV loading. Diverse post-translational modifications (PTMs) of proteins participate in the loading of specific elements into EVs. In this review, we offer a perspective on PTMs found in EVs and discuss the specific role of some PTMs, specifically Ubiquitin and Ubiquitin-like modifiers, in exosomal sorting of protein components. The understanding of these mechanisms will provide new strategies for biomedical applications. Examples include the presence of defined PTM marks on EVs as novel biomarkers for the diagnosis and prognosis of certain diseases, or the specific import of immunogenic components into EVs for vaccine generation.
    MeSH term(s) Animals ; Endosomes/metabolism ; Exosomes/metabolism ; Humans ; Lysosomes/metabolism ; Models, Biological ; Multivesicular Bodies/metabolism ; Protein Processing, Post-Translational ; Protein Transport ; Proteins/metabolism
    Chemical Substances Proteins
    Language English
    Publishing date 2017-10-27
    Publishing country Switzerland
    Document type Editorial ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1358415-7
    ISSN 1420-9071 ; 1420-682X
    ISSN (online) 1420-9071
    ISSN 1420-682X
    DOI 10.1007/s00018-017-2690-y
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 195: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  6. Article ; Online: Rapid Visualization of Intracellular Vesicle Events During Synaptic Stimulation.

    Martín-Cófreces, Noa B / Rojas-Gomez, Amelia / Dosil, Sara G / Fernandez-Delgado, Irene / Sánchez-Madrid, Francisco

    Methods in molecular biology (Clifton, N.J.)

    2020  Volume 2346, Page(s) 105–120

    Abstract: The immune synapse (IS) enables cell-cell communication between immune cells through close contacts, as well as T-cell activation and vesicle secretion. It is sustained by fine-tuned molecular interactions of receptors at both cell sides of the IS and ... ...

    Abstract The immune synapse (IS) enables cell-cell communication between immune cells through close contacts, as well as T-cell activation and vesicle secretion. It is sustained by fine-tuned molecular interactions of receptors at both cell sides of the IS and intracellular cytoskeletal components. The resulting intracellular polarization of different organelles, through cytoskeleton-guided vesicular traffic, is a key player in IS formation and signaling. We describe herein a method to analyze rapid changes of vesicle localization through microscopy analysis upon polarization toward the IS. These vesicles are monitored using the centrosome and its associated microtubular network or the actin-based structures as spatial references during the organization of the IS.
    MeSH term(s) Cell Communication/immunology ; Cell Line ; Extracellular Vesicles/immunology ; Humans ; Immunological Synapses/immunology
    Language English
    Publishing date 2020-09-08
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/7651_2020_321
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  7. Article ; Online: Natural killer (NK) cell-derived extracellular-vesicle shuttled microRNAs control T cell responses.

    Dosil, Sara G / Lopez-Cobo, Sheila / Rodriguez-Galan, Ana / Fernandez-Delgado, Irene / Ramirez-Huesca, Marta / Milan-Rois, Paula / Castellanos, Milagros / Somoza, Alvaro / Gómez, Manuel José / Reyburn, Hugh T / Vales-Gomez, Mar / Sánchez Madrid, Francisco / Fernandez-Messina, Lola

    eLife

    2022  Volume 11

    Abstract: Natural killer (NK) cells recognize and kill target cells undergoing different types of stress. NK cells are also capable of modulating immune responses. In particular, they regulate T cell functions. Small RNA next-generation sequencing of resting and ... ...

    Abstract Natural killer (NK) cells recognize and kill target cells undergoing different types of stress. NK cells are also capable of modulating immune responses. In particular, they regulate T cell functions. Small RNA next-generation sequencing of resting and activated human NK cells and their secreted extracellular vesicles (EVs) led to the identification of a specific repertoire of NK-EV-associated microRNAs and their post-transcriptional modifications signature. Several microRNAs of NK-EVs, namely miR-10b-5p, miR-92a-3p, and miR-155-5p, specifically target molecules involved in Th1 responses. NK-EVs promote the downregulation of
    MeSH term(s) Animals ; Extracellular Vesicles/metabolism ; Humans ; Killer Cells, Natural/metabolism ; Mice ; MicroRNAs/genetics ; MicroRNAs/metabolism ; RNA, Messenger/metabolism ; T-Lymphocytes/metabolism
    Chemical Substances MicroRNAs ; RNA, Messenger
    Language English
    Publishing date 2022-07-29
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.76319
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  8. Article ; Online: Extracellular vesicles from

    Izquierdo-Serrano, Raúl / Fernández-Delgado, Irene / Moreno-Gonzalo, Olga / Martín-Gayo, Enrique / Calzada-Fraile, Diego / Ramírez-Huesca, Marta / Jorge, Inmaculada / Camafeita, Emilio / Abián, Joaquín / Vicente-Manzanares, Miguel / Veiga, Esteban / Vázquez, Jesús / Sánchez-Madrid, Francisco

    Frontiers in immunology

    2022  Volume 13, Page(s) 946358

    Abstract: Communication through cell-cell contacts and extracellular vesicles (EVs) enables immune cells to coordinate their responses against diverse types of pathogens. The function exerted by EVs in this context depends on the proteins and nucleic acids loaded ... ...

    Abstract Communication through cell-cell contacts and extracellular vesicles (EVs) enables immune cells to coordinate their responses against diverse types of pathogens. The function exerted by EVs in this context depends on the proteins and nucleic acids loaded into EVs, which elicit specific responses involved in the resolution of infection. Several mechanisms control protein and nucleic acid loading into EVs; in this regard, acetylation has been described as a mechanism of cellular retention during protein sorting to exosomes. HDAC6 is a deacetylase involved in the control of cytoskeleton trafficking, organelle polarity and cell migration, defense against
    MeSH term(s) Antiviral Agents/metabolism ; Cytokines/metabolism ; Dendritic Cells ; Extracellular Vesicles/metabolism ; Humans ; Immunity, Innate ; Listeria monocytogenes ; Listeriosis ; Nucleic Acids/metabolism
    Chemical Substances Antiviral Agents ; Cytokines ; Nucleic Acids
    Language English
    Publishing date 2022-09-05
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.946358
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  9. Article ; Online: Immune synapse instructs epigenomic and transcriptomic functional reprogramming in dendritic cells.

    Alcaraz-Serna, Ana / Bustos-Morán, Eugenio / Fernández-Delgado, Irene / Calzada-Fraile, Diego / Torralba, Daniel / Marina-Zárate, Ester / Lorenzo-Vivas, Erika / Vázquez, Enrique / Barreto de Albuquerque, Juliana / Ruef, Nora / Gómez, Manuel José / Sánchez-Cabo, Fátima / Dopazo, Ana / Stein, Jens V / Ramiro, Almudena / Sánchez-Madrid, Francisco

    Science advances

    2021  Volume 7, Issue 6

    Abstract: Understanding the fate of dendritic cells (DCs) after productive immune synapses (postsynaptic DCs) with T cells during antigen presentation has been largely neglected in favor of deciphering the nuances of T cell activation and memory generation. Here, ... ...

    Abstract Understanding the fate of dendritic cells (DCs) after productive immune synapses (postsynaptic DCs) with T cells during antigen presentation has been largely neglected in favor of deciphering the nuances of T cell activation and memory generation. Here, we describe that postsynaptic DCs switch their transcriptomic signature, correlating with epigenomic changes including DNA accessibility and histone methylation. We focus on the chemokine receptor
    MeSH term(s) Cell Movement ; Dendritic Cells ; Epigenomics ; Lymph Nodes ; Receptors, CCR7 ; Synapses ; Transcriptome
    Chemical Substances Receptors, CCR7
    Language English
    Publishing date 2021-02-03
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2810933-8
    ISSN 2375-2548 ; 2375-2548
    ISSN (online) 2375-2548
    ISSN 2375-2548
    DOI 10.1126/sciadv.abb9965
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  10. Article ; Online: ISGylation controls exosome secretion by promoting lysosomal degradation of MVB proteins.

    Villarroya-Beltri, Carolina / Baixauli, Francesc / Mittelbrunn, María / Fernández-Delgado, Irene / Torralba, Daniel / Moreno-Gonzalo, Olga / Baldanta, Sara / Enrich, Carlos / Guerra, Susana / Sánchez-Madrid, Francisco

    Nature communications

    2016  Volume 7, Page(s) 13588

    Abstract: Exosomes are vesicles secreted to the extracellular environment through fusion with the plasma membrane of specific endosomes called multivesicular bodies (MVB) and mediate cell-to-cell communication in many biological processes. Posttranslational ... ...

    Abstract Exosomes are vesicles secreted to the extracellular environment through fusion with the plasma membrane of specific endosomes called multivesicular bodies (MVB) and mediate cell-to-cell communication in many biological processes. Posttranslational modifications are involved in the sorting of specific proteins into exosomes. Here we identify ISGylation as a ubiquitin-like modification that controls exosome release. ISGylation induction decreases MVB numbers and impairs exosome secretion. Using ISG15-knockout mice and mice expressing the enzymatically inactive form of the de-ISGylase USP18, we demonstrate in vitro and in vivo that ISG15 conjugation regulates exosome secretion. ISG15 conjugation triggers MVB co-localization with lysosomes and promotes the aggregation and degradation of MVB proteins. Accordingly, inhibition of lysosomal function or autophagy restores exosome secretion. Specifically, ISGylation of the MVB protein TSG101 induces its aggregation and degradation, being sufficient to impair exosome secretion. These results identify ISGylation as a novel ubiquitin-like modifier in the control of exosome production.
    MeSH term(s) Animals ; Autophagy ; Cytokines/genetics ; DNA-Binding Proteins/metabolism ; Endosomal Sorting Complexes Required for Transport/metabolism ; Exosomes/metabolism ; HEK293 Cells ; Humans ; Jurkat Cells ; Lysosomes/metabolism ; Macrophages ; Mice ; Mice, Knockout ; Multivesicular Bodies/metabolism ; T-Lymphocytes ; Transcription Factors/metabolism ; Ubiquitin Thiolesterase/metabolism ; Ubiquitins/genetics
    Chemical Substances Cytokines ; DNA-Binding Proteins ; Endosomal Sorting Complexes Required for Transport ; G1p2 protein, mouse ; Transcription Factors ; Tsg101 protein ; Ubiquitins ; ISG15 protein, human (60267-61-0) ; Usp18 protein, mouse (EC 3.4.19.-) ; Ubiquitin Thiolesterase (EC 3.4.19.12)
    Language English
    Publishing date 2016-11-24
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/ncomms13588
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