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  1. Article ; Online: Differences in exosome populations in human breast milk in relation to allergic sensitization and lifestyle.

    Torregrosa Paredes, P / Gutzeit, C / Johansson, S / Admyre, C / Stenius, F / Alm, J / Scheynius, A / Gabrielsson, S

    Allergy

    2014  Volume 69, Issue 4, Page(s) 463–471

    Abstract: Background: Breast-feeding has many beneficial effects on the developing immune system of the newborn. Breast milk contains immunoregulatory factors, such as nano-sized vesicles named exosomes. This study aimed at characterizing breast milk exosomes ... ...

    Abstract Background: Breast-feeding has many beneficial effects on the developing immune system of the newborn. Breast milk contains immunoregulatory factors, such as nano-sized vesicles named exosomes. This study aimed at characterizing breast milk exosomes from human early milk and mature milk and to investigate whether allergic sensitization and an anthroposophic lifestyle could influence the exosome profile.
    Methods: Breast milk was collected from 22 mothers at day 3-8 and from 61 mothers at 2 months postpartum, all part of the ALADDIN birth cohort. Isolated exosomes were captured on anti-MHC-class II- or anti-CD63 beads and analyzed by flow cytometry. Exosomal phenotype was related to lifestyle and allergic sensitization of the mothers, and sensitization of the child at 2 years of age.
    Results: We found a higher content of exosomes in early milk compared with mature milk. Early milk exosomes were enriched in HLA-DR molecules and displayed significantly lower levels of HLA-ABC compared with those in mature milk. Phenotypically different subpopulations of exosomes were found in mature milk. Significantly lower levels of MUC1 were detected on CD63-enriched exosomes from sensitized mothers compared with nonsensitized. Furthermore, women with an anthroposophic lifestyle had significantly lower MUC1 expression on their HLA-DR-enriched milk exosomes and up-regulated levels of CD63 on CD63-enriched exosomes compared with nonanthroposophic mothers. Notably, mothers whose children developed sensitization had an increased amount of HLA-ABC on their milk exosomes enriched for CD63.
    Conclusions: The phenotype of exosomes in breast milk varies with maternal sensitization and lifestyle, which might influence allergy development in the child.
    MeSH term(s) Adult ; Child, Preschool ; Exosomes/immunology ; Exosomes/metabolism ; Female ; Humans ; Hypersensitivity/etiology ; Life Style ; Milk, Human/immunology ; Milk, Human/metabolism ; Mucin-1/metabolism ; Phenotype ; Prospective Studies ; Tetraspanin 30/metabolism ; Time Factors
    Chemical Substances Mucin-1 ; Tetraspanin 30
    Language English
    Publishing date 2014-04
    Publishing country Denmark
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 391933-x
    ISSN 1398-9995 ; 0105-4538
    ISSN (online) 1398-9995
    ISSN 0105-4538
    DOI 10.1111/all.12357
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Immunomodulatory oligonucleotides inhibit neutrophil migration by decreasing the surface expression of interleukin-8 and leukotriene B4 receptors.

    Admyre, Charlotte / Axelsson, Lars-Göran / von Stein, Oliver / Zargari, Arezou

    Immunology

    2014  Volume 144, Issue 2, Page(s) 206–217

    Abstract: Neutrophils play important roles in many inflammatory diseases. The migration of neutrophils to the inflammatory site is tightly regulated by specific chemokines, of which interleukin-8 (IL-8) and leukotriene B4 (LTB4 ) constitute key mediators by ... ...

    Abstract Neutrophils play important roles in many inflammatory diseases. The migration of neutrophils to the inflammatory site is tightly regulated by specific chemokines, of which interleukin-8 (IL-8) and leukotriene B4 (LTB4 ) constitute key mediators by binding to the surface receptors CXCR1/2 and BLT1, respectively. Oligonucleotides (ODN) containing CpG motifs mediate potent immunomodulatory effects through binding to Toll-like receptor 9. So far, knowledge on how ODN can affect neutrophil migration during inflammation is lacking. This study demonstrates that several novel CpG ODN significantly down-regulate the surface expression of CXCR1/2 and BLT1. In addition, the ODN significantly blocked IL-8-induced and LTB4 -induced neutrophil migration in vitro, as well as leucocyte migration in vivo demonstrated in mice by intravital microscopy and in a model of airway inflammation. The down-regulation of CXCR1 is rapid, occurring 15 min after ODN stimulation, and can be mediated through an endosomally independent mechanism. Inhibition of the IL-8 and LTB4 pathways may provide new opportunities of therapeutic intervention using ODN to reduce neutrophil infiltration during inflammation.
    MeSH term(s) Animals ; Chemotaxis, Leukocyte/drug effects ; Chemotaxis, Leukocyte/immunology ; CpG Islands/genetics ; Down-Regulation/immunology ; Female ; Humans ; Immunologic Factors/pharmacology ; Immunomodulation ; Inflammation/drug therapy ; Inflammation/immunology ; Interleukin-8/antagonists & inhibitors ; Interleukin-8/biosynthesis ; Interleukin-8/immunology ; Macrophage-1 Antigen/immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Neutrophil Infiltration/drug effects ; Neutrophil Infiltration/immunology ; Neutrophils/drug effects ; Neutrophils/immunology ; Oligonucleotides/pharmacology ; Ovalbumin ; Receptors, Interleukin-8A/biosynthesis ; Receptors, Interleukin-8B/biosynthesis ; Receptors, Leukotriene B4/antagonists & inhibitors ; Receptors, Leukotriene B4/biosynthesis ; Receptors, Leukotriene B4/immunology ; Toll-Like Receptor 9/immunology ; Tumor Necrosis Factor-alpha/immunology
    Chemical Substances Immunologic Factors ; Interleukin-8 ; Macrophage-1 Antigen ; Oligonucleotides ; Receptors, Interleukin-8A ; Receptors, Interleukin-8B ; Receptors, Leukotriene B4 ; Toll-Like Receptor 9 ; Tumor Necrosis Factor-alpha ; Ovalbumin (9006-59-1)
    Language English
    Publishing date 2014-08-07
    Publishing country England
    Document type Journal Article
    ZDB-ID 80124-0
    ISSN 1365-2567 ; 0019-2805 ; 0953-4954
    ISSN (online) 1365-2567
    ISSN 0019-2805 ; 0953-4954
    DOI 10.1111/imm.12368
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Clinical efficacy of the Toll-like receptor 9 agonist cobitolimod using patient-reported-outcomes defined clinical endpoints in patients with ulcerative colitis.

    Atreya, Raja / Reinisch, Walter / Peyrin-Biroulet, Laurent / Scaldaferri, Franco / Admyre, Charlotte / Knittel, Thomas / Kowalski, Jan / Neurath, Markus Friedrich / Hawkey, Christopher

    Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver

    2018  Volume 50, Issue 10, Page(s) 1019–1029

    Abstract: Background: The Toll-like-receptor 9 (TLR-9) agonist cobitolimod (DIMS0150, Kappaproct: Aims: The objectives of this post-hoc analysis using the COLLECT study data was to investigate the clinical effects of cobitolimod using patient-reported-outcomes ...

    Abstract Background: The Toll-like-receptor 9 (TLR-9) agonist cobitolimod (DIMS0150, Kappaproct
    Aims: The objectives of this post-hoc analysis using the COLLECT study data was to investigate the clinical effects of cobitolimod using patient-reported-outcomes (PRO) defined endpoints.
    Methods: Dual topical administration of cobitolimod was studied in a randomised, multicentre clinical trial named COLLECT in moderate-to-severe UC patients. Symptomatic remission (SR) was studied in 104 patients based on their e-diary records and was defined as absence of blood in stool and a mean daily stool frequency (SF) < 4.
    Results: SR was achieved at week 4 in 17.1% of cobitolimod vs. 5.9% of placebo treated patients (p = 0.13), at week 8 in 35.7% vs. 17.6% (p = 0.07), and at week 12 in 38.6% vs. 17.6% (p = 0.04) of the patients, respectively. SR rates with cobitolimod and placebo in anti-TNFα experienced patients were smaller but with a broadly similar relative effect-size to anti-TNFα naïve patients. Clinical efficacy was higher in patients with moderate compared to severe disease.
    Conclusions: Application of the Toll-like-receptor 9 (TLR-9) agonist cobitolimod is able to induce remission as assessed by PRO measures in UC patients with moderate-to-severe activity as well as in anti-TNFα experienced and naïve patients supporting the overall efficacy of the substance.
    MeSH term(s) Administration, Topical ; Adult ; Aged ; Colitis, Ulcerative/drug therapy ; DNA/administration & dosage ; Female ; Humans ; Internationality ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Patient Reported Outcome Measures ; Retrospective Studies ; Severity of Illness Index ; Toll-Like Receptor 9/agonists ; Treatment Outcome ; Tumor Necrosis Factor-alpha/antagonists & inhibitors ; Young Adult
    Chemical Substances DIMS0150 ; Toll-Like Receptor 9 ; Tumor Necrosis Factor-alpha ; DNA (9007-49-2)
    Language English
    Publishing date 2018-06-22
    Publishing country Netherlands
    Document type Clinical Trial, Phase III ; Journal Article ; Multicenter Study ; Randomized Controlled Trial
    ZDB-ID 1459373-7
    ISSN 1878-3562 ; 1125-8055
    ISSN (online) 1878-3562
    ISSN 1125-8055
    DOI 10.1016/j.dld.2018.06.010
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Exosomes - nanovesicles with possible roles in allergic inflammation

    Admyre, C / Telemo, E / Almqvist, N / Lötvall, J / Lahesmaa, R / Scheynius, A / Gabrielsson, S

    Allergy. 2008 Apr., v. 63, no. 4

    2008  

    Abstract: Exosomes are nano-sized membrane vesicles which are released extracellularly after fusion of multivesicular endosomes with the cell membrane. Despite their characteristic composition of proteins compared to the cell membrane, no exosome-specific molecule ...

    Abstract Exosomes are nano-sized membrane vesicles which are released extracellularly after fusion of multivesicular endosomes with the cell membrane. Despite their characteristic composition of proteins compared to the cell membrane, no exosome-specific molecule has so far been characterized. Exosomes are found in bronchoalveolar lavage (BAL), urine, serum and breast milk, and are released from several cells implicated in allergy including mast cells, dendritic cells (DC), T cells and epithelial cells. Antigen-loaded exosomes have been shown to be highly immunogenic and we propose that exosomes could be a modulating factor in allergic responses. Allergen-presenting exosomes could transport allergen and stimulate allergen-specific T cells, and possibly also biasing T cell responses depending on the molecules present on the exosome surface. Furthermore, exosomes from mast cells, highly active in allergic reactions, have been found to induce DC maturation and also to be able to transport functional RNA to recipient cells, suggesting a new pathway for cell communication. Reversely, tolerizing exosomes e.g. tolerosomes, from gut or breast milk, could block an allergic response or prevent allergy development. A better understanding of the role of exosomes in allergies could make us understand how allergy can be prevented or lead to the development of more efficient treatments.
    Keywords hypersensitivity ; antigen presentation ; inflammation
    Language English
    Dates of publication 2008-04
    Size p. 404-408.
    Publisher Blackwell Publishing Ltd
    Publishing place Oxford, UK
    Document type Article
    ZDB-ID 391933-x
    ISSN 1398-9995 ; 0105-4538
    ISSN (online) 1398-9995
    ISSN 0105-4538
    DOI 10.1111/j.1398-9995.2007.01600.x
    Database NAL-Catalogue (AGRICOLA)

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  5. Article ; Online: Exosomes - nanovesicles with possible roles in allergic inflammation.

    Admyre, C / Telemo, E / Almqvist, N / Lötvall, J / Lahesmaa, R / Scheynius, A / Gabrielsson, S

    Allergy

    2008  Volume 63, Issue 4, Page(s) 404–408

    Abstract: Exosomes are nano-sized membrane vesicles which are released extracellularly after fusion of multivesicular endosomes with the cell membrane. Despite their characteristic composition of proteins compared to the cell membrane, no exosome-specific molecule ...

    Abstract Exosomes are nano-sized membrane vesicles which are released extracellularly after fusion of multivesicular endosomes with the cell membrane. Despite their characteristic composition of proteins compared to the cell membrane, no exosome-specific molecule has so far been characterized. Exosomes are found in bronchoalveolar lavage (BAL), urine, serum and breast milk, and are released from several cells implicated in allergy including mast cells, dendritic cells (DC), T cells and epithelial cells. Antigen-loaded exosomes have been shown to be highly immunogenic and we propose that exosomes could be a modulating factor in allergic responses. Allergen-presenting exosomes could transport allergen and stimulate allergen-specific T cells, and possibly also biasing T cell responses depending on the molecules present on the exosome surface. Furthermore, exosomes from mast cells, highly active in allergic reactions, have been found to induce DC maturation and also to be able to transport functional RNA to recipient cells, suggesting a new pathway for cell communication. Reversely, tolerizing exosomes e.g. tolerosomes, from gut or breast milk, could block an allergic response or prevent allergy development. A better understanding of the role of exosomes in allergies could make us understand how allergy can be prevented or lead to the development of more efficient treatments.
    MeSH term(s) Animals ; Cytoplasmic Vesicles/immunology ; Humans ; Hypersensitivity/immunology ; Immune Tolerance ; Inflammation/immunology
    Language English
    Publishing date 2008-04
    Publishing country Denmark
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 391933-x
    ISSN 1398-9995 ; 0105-4538
    ISSN (online) 1398-9995
    ISSN 0105-4538
    DOI 10.1111/j.1398-9995.2007.01600.x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: The TLR9 Agonist Cobitolimod Induces IL10-Producing Wound Healing Macrophages and Regulatory T Cells in Ulcerative Colitis.

    Schmitt, Heike / Ulmschneider, Julia / Billmeier, Ulrike / Vieth, Michael / Scarozza, Patrizio / Sonnewald, Sophia / Reid, Stephen / Atreya, Imke / Rath, Timo / Zundler, Sebastian / Langheinrich, Melanie / Schüttler, Jürgen / Hartmann, Arndt / Winkler, Thomas / Admyre, Charlotte / Knittel, Thomas / Dieterich Johansson, Christine / Zargari, Arezou / Neurath, Markus F /
    Atreya, Raja

    Journal of Crohn's & colitis

    2019  Volume 14, Issue 4, Page(s) 508–524

    Abstract: Background and aims: The topically applied Toll-like receptor 9 [TLR9] agonist cobitolimod is a first-in-class DNA-based oligonucleotide with demonstrated therapeutic efficacy in clinical trials with ulcerative colitis [UC] patients. We here ... ...

    Abstract Background and aims: The topically applied Toll-like receptor 9 [TLR9] agonist cobitolimod is a first-in-class DNA-based oligonucleotide with demonstrated therapeutic efficacy in clinical trials with ulcerative colitis [UC] patients. We here characterized its anti-inflammatory mechanism in UC.
    Methods: Luminal cobitolimod administration was evaluated in an experimental dextran sodium sulfate [DSS]-induced colitis model. Cultured blood and mucosal cells from UC patients were treated with cobitolimod and analysed via microarray, quantitative real-time PCR, ELISA and flow cytometry. Intestinal slides of cobitolimod-treated UC patients were analysed by immunohistochemistry.
    Results: Cobitolimod administration markedly suppressed experimental colitis activity, and microarray analyses demonstrated mucosal IL10 upregulation and suppression of IL17 signalling pathways. Cobitolimod treatment was associated with significant induction of mucosal IL10+Tr1 and Treg cells and suppression of Th17 cells. TLR9 knockout mice indicated that cobitolimod requires TLR9 signalling for IL10 induction. In UC patients, mucosal TLR9 levels correlated with severity of inflammation. Cobitolimod inhibited IL17A and IL17F, but increased IL10 and FoxP3 expression in cultured intestinal UC T cells. Cobitolimod-mediated suppression of intestinal IL17+T cells was abrogated by IL10 blockade. Furthermore, cobitolimod led to heightened IL10 production by wound healing macrophages. Immunohistochemistry in intestinal biopsies of cobitolimod-treated UC patients indicated increased presence of IL10+mononuclear and regulatory T cells, as well as reduction of IL17+cells.
    Conclusion: Activation of TLR9 via cobitolimod might represent a novel therapeutic approach in UC, as it suppresses Th17 cells and induces anti-inflammatory IL10+macrophages and regulatory T cells, thereby modifying the dysregulated intestinal cytokine balance.
    Podcast: This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast.
    MeSH term(s) Animals ; Anti-Inflammatory Agents/administration & dosage ; Anti-Inflammatory Agents/pharmacokinetics ; Cell Culture Techniques ; Colitis, Ulcerative/drug therapy ; Colitis, Ulcerative/immunology ; Colitis, Ulcerative/pathology ; Disease Models, Animal ; Female ; Gastrointestinal Agents/administration & dosage ; Gastrointestinal Agents/pharmacokinetics ; Gene Expression Regulation ; Humans ; Immunomodulation ; Interleukin-10/analysis ; Interleukin-17/analysis ; Intestinal Mucosa/drug effects ; Intestinal Mucosa/immunology ; Intestinal Mucosa/pathology ; Macrophages/drug effects ; Macrophages/immunology ; Macrophages/pathology ; Male ; Mice ; Middle Aged ; Oligodeoxyribonucleotides/administration & dosage ; Oligodeoxyribonucleotides/pharmacokinetics ; T-Lymphocytes, Regulatory/drug effects ; T-Lymphocytes, Regulatory/immunology ; Th17 Cells/drug effects ; Th17 Cells/immunology ; Tissue Array Analysis/methods ; Toll-Like Receptor 9/agonists
    Chemical Substances Anti-Inflammatory Agents ; Gastrointestinal Agents ; Interleukin-17 ; Oligodeoxyribonucleotides ; TLR9 protein, human ; Toll-Like Receptor 9 ; Interleukin-10 (130068-27-8) ; cobitolimod (328101264R)
    Language English
    Publishing date 2019-08-24
    Publishing country England
    Document type Clinical Trial, Phase II ; Journal Article ; Randomized Controlled Trial
    ZDB-ID 2390120-2
    ISSN 1876-4479 ; 1873-9946
    ISSN (online) 1876-4479
    ISSN 1873-9946
    DOI 10.1093/ecco-jcc/jjz170
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Bronchoalveolar lavage fluid exosomes contribute to cytokine and leukotriene production in allergic asthma.

    Torregrosa Paredes, P / Esser, J / Admyre, C / Nord, M / Rahman, Q K / Lukic, A / Rådmark, O / Grönneberg, R / Grunewald, J / Eklund, A / Scheynius, A / Gabrielsson, S

    Allergy

    2012  Volume 67, Issue 7, Page(s) 911–919

    Abstract: Background: Leukotrienes (LTs) are potent pro-inflammatory mediators involved in asthma. Exosomes, nanosized vesicles released from various cells, can stimulate or down-regulate immune responses, depending on the state and nature of the originating cell. ...

    Abstract Background: Leukotrienes (LTs) are potent pro-inflammatory mediators involved in asthma. Exosomes, nanosized vesicles released from various cells, can stimulate or down-regulate immune responses, depending on the state and nature of the originating cell. We have recently shown an altered exosome profile in bronchoalveolar lavage fluid (BALF) of patients with sarcoidosis, but their role in asthma is unknown. Our aims were to investigate whether exosomes from BALF have LT biosynthetic capacity and to explore phenotypic and functional characteristics of BALF exosomes in asthma.
    Methods: Bronchoalveolar lavage fluid exosomes were collected from healthy individuals (n = 13) and patients with mild allergic asthma to birch pollen (n = 12) before and after birch allergen provocation. Exosomes were characterized by flow cytometry and Western blot. Their capacity to induce IL-8 and LT production in the human bronchial epithelial cell (BEC) line 16HB14o- was measured by ELISA and reverse-phase HPLC, respectively.
    Results: Compared to BALF exosomes from healthy individuals, BALF exosomes from asthmatics displayed higher levels of exosome-associated markers, such as the tetraspanins CD63 and CD81 and the scavenger receptor CD36. No major differences were observed between BALF exosomes from before and after allergen provocation. Furthermore, we show that BALF exosomes contain enzymes for LT biosynthesis. The effect of exosomes to promote LTC(4) and IL-8 release in BEC was significantly increased for exosomes from asthmatics, and the CysLT(1) receptor antagonist Montelukast reduced exosome-induced IL-8 secretion.
    Conclusions: Bronchoalveolar lavage fluid exosomes from asthmatic and healthy individuals exhibit distinct phenotypes and functions. BALF exosomes from asthmatics might contribute to subclinical inflammation by increasing cytokine and LTC(4) generation in airway epithelium.
    MeSH term(s) Acetates/pharmacology ; Adult ; Allergens/immunology ; Anti-Asthmatic Agents/pharmacology ; Asthma/immunology ; Bronchi/immunology ; Bronchi/metabolism ; Bronchoalveolar Lavage Fluid/immunology ; Cytokines/biosynthesis ; Cytokines/immunology ; Eosinophils/immunology ; Epithelial Cells/metabolism ; Exosomes/drug effects ; Exosomes/immunology ; Exosomes/metabolism ; Female ; Humans ; Leukotrienes/biosynthesis ; Leukotrienes/immunology ; Male ; Middle Aged ; Quinolines/pharmacology ; Young Adult
    Chemical Substances Acetates ; Allergens ; Anti-Asthmatic Agents ; Cytokines ; Leukotrienes ; Quinolines ; montelukast (MHM278SD3E)
    Language English
    Publishing date 2012-07
    Publishing country Denmark
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 391933-x
    ISSN 1398-9995 ; 0105-4538
    ISSN (online) 1398-9995
    ISSN 0105-4538
    DOI 10.1111/j.1398-9995.2012.02835.x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Different types of in vitro generated human monocyte-derived dendritic cells release exosomes with distinct phenotypes.

    Johansson, Sara M / Admyre, Charlotte / Scheynius, Annika / Gabrielsson, Susanne

    Immunology

    2007  Volume 123, Issue 4, Page(s) 491–499

    Abstract: Human in vitro generated dendritic cells and the exosomes they release are potential tools for the modulation of immune responses. Here, we characterized differently generated monocyte-derived dendritic cells (MDDCs) and their exosomes. Culturing of ... ...

    Abstract Human in vitro generated dendritic cells and the exosomes they release are potential tools for the modulation of immune responses. Here, we characterized differently generated monocyte-derived dendritic cells (MDDCs) and their exosomes. Culturing of peripheral CD14+ cells from the same individuals with either interleukin (IL)-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF) (conventional MDDCs) or alternatively with IL-4 and IL-3 generated immature MDDCs in 7 days. Fluorescence-activated cell sorting (FACS) analysis showed that the IL-4/IL-3-generated MDDCs had significantly lower percentages of CD1a+, CD40+ and CD80+ cells and a higher percentage of CD86+ cells as compared with conventional MDDCs. In addition, IL-4/IL-3-generated MDDCs had significantly higher densities of major histocompatibility complex (MHC) class I [human leucocyte antigen (HLA)-ABC], MHC class II (HLA-DR), CD11c and the tetraspanin CD81 as compared with conventional MDDCs. In a comparison of their ability to stimulate CD8+ T cells, we found that the IL-4/IL-3 MDDCs were slightly more efficient than the conventional MDDCs at inducing interferon (IFN)-gamma release in response to viral peptides. Exosome morphology was confirmed by electron microscopy and exosome phenotypes were analysed by flow cytometry and western blot. In comparison to exosomes from conventional MDDCs, exosomes from IL-4/IL-3-generated MDDCs showed significantly stronger signals for HLA-ABC, HLA-DR, CD11c, CD63 and CD81. Thus, phenotypically the exosomes largely reflected their MDDCs of origin. When exosomes were loaded with viral peptides, both types of exosomes induced IFN-gamma release from CD8+ T cells. Our findings might have significance for the development of DC- and exosome-based therapies.
    MeSH term(s) Antigen Presentation ; Antigens, Viral/immunology ; CD8-Positive T-Lymphocytes/immunology ; Cells, Cultured ; Cytoplasmic Vesicles/immunology ; Cytoplasmic Vesicles/ultrastructure ; Dendritic Cells/immunology ; Dendritic Cells/ultrastructure ; Enzyme-Linked Immunosorbent Assay/methods ; HLA-DR Antigens/metabolism ; Humans ; Interferon-gamma/biosynthesis ; Interleukin-3/immunology ; Interleukin-4/immunology ; Lymphocyte Activation/immunology ; Monocytes/immunology
    Chemical Substances Antigens, Viral ; HLA-DR Antigens ; Interleukin-3 ; Interleukin-4 (207137-56-2) ; Interferon-gamma (82115-62-6)
    Language English
    Publishing date 2007-10-19
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80124-0
    ISSN 1365-2567 ; 0019-2805 ; 0953-4954
    ISSN (online) 1365-2567
    ISSN 0019-2805 ; 0953-4954
    DOI 10.1111/j.1365-2567.2007.02714.x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Direct exosome stimulation of peripheral human T cells detected by ELISPOT.

    Admyre, Charlotte / Johansson, Sara M / Paulie, Staffan / Gabrielsson, Susanne

    European journal of immunology

    2006  Volume 36, Issue 7, Page(s) 1772–1781

    Abstract: Exosomes from APC are nano-vesicles that can induce antigen-specific T cell responses and are presently explored as therapeutic tools in different clinical settings. Investigations of the capacity of exosomes to stimulate T cells in vitro have mostly ... ...

    Abstract Exosomes from APC are nano-vesicles that can induce antigen-specific T cell responses and are presently explored as therapeutic tools in different clinical settings. Investigations of the capacity of exosomes to stimulate T cells in vitro have mostly been performed on T cell hybridomas, clones or lines. Whether exosomes can stimulate T cells directly or need the presence of dendritic cells (DC) is debated. We could detect exosome-induced antigen-specific CD8(+) T cell responses in peripheral blood from humans. Exosomes from monocyte-derived DC (MDDC) were loaded with a mix of 23 immunogenic peptides from EBV, CMV and influenza virus, and added to autologous peripheral CD8(+) T cells. IFN-gamma-producing cells were detected by enzyme-linked immunospot assay (ELISPOT). MDDC-exosomes induced IFN-gamma production in CD8(+) T cells without addition of DC. The response was exosome dose dependent, and dependent on exosomal MHC class I. Furthermore, we detected an enhanced T cell stimulatory capacity by exosomes from lipopolysaccharide-matured MDDC compared to exosomes from immature MDDC. Exosomes could also induce TNF-alpha production. These results show, for the first time, that exosomes can directly stimulate human peripheral CD8(+) T cells in an antigen-specific manner and that ELISPOT is a suitable method for detecting exosome-induced peripheral T cell responses. This system may provide a useful tool when developing exosomes as therapeutic agents.
    MeSH term(s) Cells, Cultured ; Cytoplasmic Vesicles/immunology ; Cytoplasmic Vesicles/ultrastructure ; Dendritic Cells/immunology ; Dendritic Cells/ultrastructure ; Enzyme-Linked Immunosorbent Assay/methods ; Humans ; Lymphocyte Activation/immunology ; Microscopy, Immunoelectron ; T-Lymphocytes/immunology
    Language English
    Publishing date 2006-07
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 120108-6
    ISSN 1521-4141 ; 0014-2980
    ISSN (online) 1521-4141
    ISSN 0014-2980
    DOI 10.1002/eji.200535615
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Topical treatment with the Toll-like receptor agonist DIMS0150 has potential for lasting relief of symptoms in patients with chronic active ulcerative colitis by restoring glucocorticoid sensitivity.

    Musch, Eugen / Lutfi, Tamim / von Stein, Petra / Zargari, Arezou / Admyre, Charlotte / Malek, Mouhamad / Löfberg, Robert / von Stein, Oliver D

    Inflammatory bowel diseases

    2011  Volume 19, Issue 2, Page(s) 283–292

    Abstract: Background: Patients with chronic active ulcerative colitis (UC) are regarded as treatment failures and represent an area of high unmet medical need, as normally the only remaining option is colectomy.: Methods: We treated a total of eight chronic ... ...

    Abstract Background: Patients with chronic active ulcerative colitis (UC) are regarded as treatment failures and represent an area of high unmet medical need, as normally the only remaining option is colectomy.
    Methods: We treated a total of eight chronic active severe UC outpatients with the immunomodulatory agent DIMS0150 as an add-on to current therapies. Seven patients received a single topical dose of 30 mg and one special case subject received three doses with 4 weeks between dosing occasions. All patients were classed as treatment failures and were elected for colectomy. Efficacy evaluation was determined in terms of colitis activity index, endoscopic improvement, and histologic disease activity assessed primarily at week 12 with a follow-up period of over 2 years. Glucocorticoid sensitivity was assayed by in vitro measurement of interleukin 6.
    Results: All patients demonstrated a pronounced and rapid reduction in their colitis activity index within 1 week following a single intracolonic administration via colonoscope of the agent DIMS0150. Further improvements were evident at week 4, resulting in a clinical response rate for the single-dose treatment of 71%, with 43% in clinical remission. By week 12 the clinical response and remission rates had reached 82% and 71%, respectively. A follow-up period of over 2 years posttreatment indicated that all but one of the treated patients had avoided the need for colectomy, with the longest patient being in symptom-free remission for over 27 months. Treatment with DIMS0150 restored glucocorticoid sensitivity.
    Conclusions: DIMS0150 may have the potential to be an effective agent to treat chronic active UC patients with the prospect to avoid colectomy on a long-term basis and is currently the subject of a clinical phase III study (EudraCT number: 2011-003130-14).
    MeSH term(s) Administration, Topical ; Adult ; Aged ; Biomarkers/blood ; Colitis, Ulcerative/drug therapy ; Colitis, Ulcerative/metabolism ; Colon/metabolism ; Colonoscopy ; DNA/therapeutic use ; Drug Administration Schedule ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Glucocorticoids/therapeutic use ; Humans ; Immunologic Factors/therapeutic use ; Interleukin-6/blood ; Male ; Middle Aged ; Prednisolone/therapeutic use ; Prospective Studies ; Toll-Like Receptor 9/metabolism ; Treatment Outcome
    Chemical Substances Biomarkers ; DIMS0150 ; Glucocorticoids ; IL6 protein, human ; Immunologic Factors ; Interleukin-6 ; TLR9 protein, human ; Toll-Like Receptor 9 ; DNA (9007-49-2) ; Prednisolone (9PHQ9Y1OLM)
    Language English
    Publishing date 2011-08-29
    Publishing country England
    Document type Clinical Trial ; Journal Article
    ZDB-ID 1340971-2
    ISSN 1536-4844 ; 1078-0998
    ISSN (online) 1536-4844
    ISSN 1078-0998
    DOI 10.1002/ibd.23019
    Database MEDical Literature Analysis and Retrieval System OnLINE

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