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  1. Article ; Online: From the Deep Sea to Everywhere: Environmental Antigens for iNKT Cells.

    Wingender, Gerhard

    Archivum immunologiae et therapiae experimentalis

    2016  Volume 64, Issue 4, Page(s) 291–298

    Abstract: Invariant natural killer T (iNKT) cells are a unique subset of innate T cells that share features with innate NK cells and adaptive memory T cells. The first iNKT cell antigen described was found 1993 in a marine sponge and it took over 10 years for ... ...

    Abstract Invariant natural killer T (iNKT) cells are a unique subset of innate T cells that share features with innate NK cells and adaptive memory T cells. The first iNKT cell antigen described was found 1993 in a marine sponge and it took over 10 years for other, bacterial antigens to be described. Given the paucity of known bacterial iNKT cell antigens, it appeared as if iNKT cells play a very specialist role in the protection against few, rare and unusual pathogenic bacteria. However, in the last few years several publications painted a very different picture, suggesting that antigens for iNKT cells are found almost ubiquitous in the environment. These environmental iNKT cell antigens can shape the distribution, phenotype and function of iNKT cells. Here, these recent findings will be reviewed and their implications for the field will be outlined.
    MeSH term(s) Animals ; Antigens/chemistry ; Cytokines/immunology ; Cytokines/metabolism ; Environment ; Homeostasis ; Humans ; Immunity, Innate ; Intestines/immunology ; Lymphocyte Activation/immunology ; Mucous Membrane/immunology ; Mucous Membrane/microbiology ; Natural Killer T-Cells/immunology ; Phenotype ; Porifera ; Signal Transduction/immunology ; Symbiosis ; T-Lymphocyte Subsets/immunology
    Chemical Substances Antigens ; Cytokines
    Language English
    Publishing date 2016-08
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 282209-x
    ISSN 1661-4917 ; 0004-069X
    ISSN (online) 1661-4917
    ISSN 0004-069X
    DOI 10.1007/s00005-015-0381-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The IL-10GFP (VeRT-X) mouse strain is not suitable for the detection of IL-10 production by granulocytes during lung inflammation.

    Özkan, Müge / Eskiocak, Yusuf Cem / Wingender, Gerhard

    PloS one

    2021  Volume 16, Issue 5, Page(s) e0247895

    Abstract: The clear and unequivocal identification of immune effector functions is essential to understand immune responses. The cytokine IL-10 is a critical immune regulator and was shown, for example, to limit pathology during various lung diseases. However, the ...

    Abstract The clear and unequivocal identification of immune effector functions is essential to understand immune responses. The cytokine IL-10 is a critical immune regulator and was shown, for example, to limit pathology during various lung diseases. However, the clear identification of IL-10-producing cells is challenging and, therefore, reporter mouse lines were developed to facilitate their detection. Several such reporter lines utilize GFP, including the IL-10GFP (VeRT-X) reporter strain studied here. In line with previous reports, we found that this IL-10GFP line faithfully reports on the IL-10 production of lymphoid cells. However, we show that the IL-10GFP reporter is not suitable to analyse IL-10 production of myeloid cells during inflammation. During inflammation, the autofluorescence of myeloid cells increased to an extent that entirely masked the IL-10-specific GFP-signal. Our data illustrate a general and important technical caveat using GFP-reporter lines for the analysis of myeloid cells and suggest that previous reports on effector functions of myeloid cells using such GFP-based reporters might require re-evaluation.
    MeSH term(s) Animals ; Flow Cytometry ; Granulocytes/metabolism ; Interleukin-10/metabolism ; Mice ; Mice, Inbred C57BL ; Myeloid Cells/metabolism ; Pneumonia/metabolism
    Chemical Substances Interleukin-10 (130068-27-8)
    Language English
    Publishing date 2021-05-12
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0247895
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Macrophage and dendritic cell subset composition can distinguish endotypes in adjuvant-induced asthma mouse models.

    Özkan, Müge / Eskiocak, Yusuf Cem / Wingender, Gerhard

    PloS one

    2021  Volume 16, Issue 6, Page(s) e0250533

    Abstract: Asthma is a heterogeneous disease with neutrophilic and eosinophilic asthma as the main endotypes that are distinguished according to the cells recruited to the airways and the related pathology. Eosinophilic asthma is the treatment-responsive endotype, ... ...

    Abstract Asthma is a heterogeneous disease with neutrophilic and eosinophilic asthma as the main endotypes that are distinguished according to the cells recruited to the airways and the related pathology. Eosinophilic asthma is the treatment-responsive endotype, which is mainly associated with allergic asthma. Neutrophilic asthma is a treatment-resistant endotype, affecting 5-10% of asthmatics. Although eosinophilic asthma is well-studied, a clear understanding of the endotypes is essential to devise effective diagnosis and treatment approaches for neutrophilic asthma. To this end, we directly compared adjuvant-induced mouse models of neutrophilic (CFA/OVA) and eosinophilic (Alum/OVA) asthma side-by-side. The immune response in the inflamed lung was analyzed by multi-parametric flow cytometry and immunofluorescence. We found that eosinophilic asthma was characterized by a preferential recruitment of interstitial macrophages and myeloid dendritic cells, whereas in neutrophilic asthma plasmacytoid dendritic cells, exudate macrophages, and GL7+ activated B cells predominated. This differential distribution of macrophage and dendritic cell subsets reveals important aspects of the pathophysiology of asthma and holds the promise to be used as biomarkers to diagnose asthma endotypes.
    MeSH term(s) Animals ; Asthma/immunology ; Dendritic Cells/cytology ; Disease Models, Animal ; Leukocyte Count ; Macrophages/cytology ; Mice ; Neutrophils/immunology
    Language English
    Publishing date 2021-06-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0250533
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: The interaction between invariant Natural Killer T cells and the mucosal microbiota.

    Hapil, Fatma Zehra / Wingender, Gerhard

    Immunology

    2018  Volume 155, Issue 2, Page(s) 164–175

    Abstract: The surface of mammalian bodies is colonized by a multitude of microbial organisms, which under normal conditions support the host and are considered beneficial commensals. This requires, however, that the composition of the commensal microbiota is ... ...

    Abstract The surface of mammalian bodies is colonized by a multitude of microbial organisms, which under normal conditions support the host and are considered beneficial commensals. This requires, however, that the composition of the commensal microbiota is tightly controlled and regulated. The host immune system plays an important role in the maintenance of this microbiota composition. Here we focus on the contribution of one particular immune cell type, invariant Natural Killer T (iNKT) cells, in this process. The iNKT cells are a unique subset of T cells characterized by two main features. First, they express an invariant T-cell receptor that recognizes glycolipid antigens presented by CD1d, a non-polymorphic major histocompatibility complex class I-like molecule. Second, iNKT cells develop as effector/memory cells and swiftly exert effector functions, like cytokine production and cytotoxicity, after activation. We outline the influence that the mucosal microbiota can have on iNKT cells, and how iNKT cells contribute to the maintenance of the microbiota composition.
    MeSH term(s) Animals ; Gastrointestinal Microbiome/immunology ; Host-Pathogen Interactions/immunology ; Humans ; Immune System ; Intestinal Mucosa/immunology ; Intestinal Mucosa/metabolism ; Intestinal Mucosa/microbiology ; Microbiota ; Mucous Membrane/immunology ; Mucous Membrane/metabolism ; Mucous Membrane/microbiology ; Natural Killer T-Cells/immunology ; Natural Killer T-Cells/metabolism ; Respiratory Mucosa/immunology ; Respiratory Mucosa/metabolism ; Respiratory Mucosa/microbiology
    Language English
    Publishing date 2018-07-11
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 80124-0
    ISSN 1365-2567 ; 0019-2805 ; 0953-4954
    ISSN (online) 1365-2567
    ISSN 0019-2805 ; 0953-4954
    DOI 10.1111/imm.12958
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: The IL-10GFP (VeRT-X) mouse strain is not suitable for the detection of IL-10 production by granulocytes during lung inflammation.

    Müge Özkan / Yusuf Cem Eskiocak / Gerhard Wingender

    PLoS ONE, Vol 16, Iss 5, p e

    2021  Volume 0247895

    Abstract: The clear and unequivocal identification of immune effector functions is essential to understand immune responses. The cytokine IL-10 is a critical immune regulator and was shown, for example, to limit pathology during various lung diseases. However, the ...

    Abstract The clear and unequivocal identification of immune effector functions is essential to understand immune responses. The cytokine IL-10 is a critical immune regulator and was shown, for example, to limit pathology during various lung diseases. However, the clear identification of IL-10-producing cells is challenging and, therefore, reporter mouse lines were developed to facilitate their detection. Several such reporter lines utilize GFP, including the IL-10GFP (VeRT-X) reporter strain studied here. In line with previous reports, we found that this IL-10GFP line faithfully reports on the IL-10 production of lymphoid cells. However, we show that the IL-10GFP reporter is not suitable to analyse IL-10 production of myeloid cells during inflammation. During inflammation, the autofluorescence of myeloid cells increased to an extent that entirely masked the IL-10-specific GFP-signal. Our data illustrate a general and important technical caveat using GFP-reporter lines for the analysis of myeloid cells and suggest that previous reports on effector functions of myeloid cells using such GFP-based reporters might require re-evaluation.
    Keywords Medicine ; R ; Science ; Q
    Subject code 616
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Macrophage and dendritic cell subset composition can distinguish endotypes in adjuvant-induced asthma mouse models.

    Müge Özkan / Yusuf Cem Eskiocak / Gerhard Wingender

    PLoS ONE, Vol 16, Iss 6, p e

    2021  Volume 0250533

    Abstract: Asthma is a heterogeneous disease with neutrophilic and eosinophilic asthma as the main endotypes that are distinguished according to the cells recruited to the airways and the related pathology. Eosinophilic asthma is the treatment-responsive endotype, ... ...

    Abstract Asthma is a heterogeneous disease with neutrophilic and eosinophilic asthma as the main endotypes that are distinguished according to the cells recruited to the airways and the related pathology. Eosinophilic asthma is the treatment-responsive endotype, which is mainly associated with allergic asthma. Neutrophilic asthma is a treatment-resistant endotype, affecting 5-10% of asthmatics. Although eosinophilic asthma is well-studied, a clear understanding of the endotypes is essential to devise effective diagnosis and treatment approaches for neutrophilic asthma. To this end, we directly compared adjuvant-induced mouse models of neutrophilic (CFA/OVA) and eosinophilic (Alum/OVA) asthma side-by-side. The immune response in the inflamed lung was analyzed by multi-parametric flow cytometry and immunofluorescence. We found that eosinophilic asthma was characterized by a preferential recruitment of interstitial macrophages and myeloid dendritic cells, whereas in neutrophilic asthma plasmacytoid dendritic cells, exudate macrophages, and GL7+ activated B cells predominated. This differential distribution of macrophage and dendritic cell subsets reveals important aspects of the pathophysiology of asthma and holds the promise to be used as biomarkers to diagnose asthma endotypes.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: The Ca2+ concentration impacts the cytokine production of mouse and human lymphoid cells and the polarization of human macrophages in vitro.

    Eskiocak, Yusuf Cem / Ayyildiz, Zeynep Ozge / Gunalp, Sinem / Korkmaz, Asli / Helvaci, Derya Goksu / Dogan, Yavuz / Sag, Duygu / Wingender, Gerhard

    PloS one

    2023  Volume 18, Issue 2, Page(s) e0282037

    Abstract: Various aspects of the in vitro culture conditions can impact the functional response of immune cells. For example, it was shown that a Ca2+ concentration of at least 1.5 mM during in vitro stimulation is needed for optimal cytokine production by ... ...

    Abstract Various aspects of the in vitro culture conditions can impact the functional response of immune cells. For example, it was shown that a Ca2+ concentration of at least 1.5 mM during in vitro stimulation is needed for optimal cytokine production by conventional αβ T cells. Here we extend these findings by showing that also unconventional T cells (invariant Natural Killer T cells, mucosal-associated invariant T cells, γδ T cells), as well as B cells, show an increased cytokine response following in vitro stimulation in the presence of elevated Ca2+ concentrations. This effect appeared more pronounced with mouse than with human lymphoid cells and did not influence their survival. A similarly increased cytokine response due to elevated Ca2+ levels was observed with primary human monocytes. In contrast, primary human monocyte-derived macrophages, either unpolarized (M0) or polarized into M1 or M2 macrophages, displayed increased cell death in the presence of elevated Ca2+ concentrations. Furthermore, elevated Ca2+ concentrations promoted phenotypic M1 differentiation by increasing M1 markers on M1 and M2 macrophages and decreasing M2 markers on M2 macrophages. However, the cytokine production of macrophages, again in contrast to the lymphoid cells, was unaltered by the Ca2+ concentration. In summary, our data demonstrate that the Ca2+ concentration during in vitro cultures is an important variable to be considered for functional experiments and that elevated Ca2+ levels can boost cytokine production by both mouse and human lymphoid cells.
    MeSH term(s) Humans ; Calcium/metabolism ; Macrophages/metabolism ; Cytokines/metabolism ; Monocytes/metabolism ; Cell Differentiation ; Lymphocytes/metabolism
    Chemical Substances Calcium (SY7Q814VUP) ; Cytokines
    Language English
    Publishing date 2023-02-24
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0282037
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: The Ca2+ concentration impacts the cytokine production of mouse and human lymphoid cells and the polarization of human macrophages in vitro

    Yusuf Cem Eskiocak / Zeynep Ozge Ayyildiz / Sinem Gunalp / Asli Korkmaz / Derya Goksu Helvaci / Yavuz Dogan / Duygu Sag / Gerhard Wingender

    PLoS ONE, Vol 18, Iss

    2023  Volume 2

    Abstract: Various aspects of the in vitro culture conditions can impact the functional response of immune cells. For example, it was shown that a Ca2+ concentration of at least 1.5 mM during in vitro stimulation is needed for optimal cytokine production by ... ...

    Abstract Various aspects of the in vitro culture conditions can impact the functional response of immune cells. For example, it was shown that a Ca2+ concentration of at least 1.5 mM during in vitro stimulation is needed for optimal cytokine production by conventional αβ T cells. Here we extend these findings by showing that also unconventional T cells (invariant Natural Killer T cells, mucosal-associated invariant T cells, γδ T cells), as well as B cells, show an increased cytokine response following in vitro stimulation in the presence of elevated Ca2+ concentrations. This effect appeared more pronounced with mouse than with human lymphoid cells and did not influence their survival. A similarly increased cytokine response due to elevated Ca2+ levels was observed with primary human monocytes. In contrast, primary human monocyte-derived macrophages, either unpolarized (M0) or polarized into M1 or M2 macrophages, displayed increased cell death in the presence of elevated Ca2+ concentrations. Furthermore, elevated Ca2+ concentrations promoted phenotypic M1 differentiation by increasing M1 markers on M1 and M2 macrophages and decreasing M2 markers on M2 macrophages. However, the cytokine production of macrophages, again in contrast to the lymphoid cells, was unaltered by the Ca2+ concentration. In summary, our data demonstrate that the Ca2+ concentration during in vitro cultures is an important variable to be considered for functional experiments and that elevated Ca2+ levels can boost cytokine production by both mouse and human lymphoid cells.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: The Ca2+ concentration impacts the cytokine production of mouse and human lymphoid cells and the polarization of human macrophages in vitro.

    Yusuf Cem Eskiocak / Zeynep Ozge Ayyildiz / Sinem Gunalp / Asli Korkmaz / Derya Goksu Helvaci / Yavuz Dogan / Duygu Sag / Gerhard Wingender

    PLoS ONE, Vol 18, Iss 2, p e

    2023  Volume 0282037

    Abstract: Various aspects of the in vitro culture conditions can impact the functional response of immune cells. For example, it was shown that a Ca2+ concentration of at least 1.5 mM during in vitro stimulation is needed for optimal cytokine production by ... ...

    Abstract Various aspects of the in vitro culture conditions can impact the functional response of immune cells. For example, it was shown that a Ca2+ concentration of at least 1.5 mM during in vitro stimulation is needed for optimal cytokine production by conventional αβ T cells. Here we extend these findings by showing that also unconventional T cells (invariant Natural Killer T cells, mucosal-associated invariant T cells, γδ T cells), as well as B cells, show an increased cytokine response following in vitro stimulation in the presence of elevated Ca2+ concentrations. This effect appeared more pronounced with mouse than with human lymphoid cells and did not influence their survival. A similarly increased cytokine response due to elevated Ca2+ levels was observed with primary human monocytes. In contrast, primary human monocyte-derived macrophages, either unpolarized (M0) or polarized into M1 or M2 macrophages, displayed increased cell death in the presence of elevated Ca2+ concentrations. Furthermore, elevated Ca2+ concentrations promoted phenotypic M1 differentiation by increasing M1 markers on M1 and M2 macrophages and decreasing M2 markers on M2 macrophages. However, the cytokine production of macrophages, again in contrast to the lymphoid cells, was unaltered by the Ca2+ concentration. In summary, our data demonstrate that the Ca2+ concentration during in vitro cultures is an important variable to be considered for functional experiments and that elevated Ca2+ levels can boost cytokine production by both mouse and human lymphoid cells.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article: The Role of TRAIL/DRs in the Modulation of Immune Cells and Responses.

    Sag, Duygu / Ayyildiz, Zeynep Ozge / Gunalp, Sinem / Wingender, Gerhard

    Cancers

    2019  Volume 11, Issue 10

    Abstract: Expression of TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) by immune cells can lead to the induction of apoptosis in tumor cells. However, it becomes increasingly clear that the interaction of TRAIL and its death receptors (DRs) can ... ...

    Abstract Expression of TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) by immune cells can lead to the induction of apoptosis in tumor cells. However, it becomes increasingly clear that the interaction of TRAIL and its death receptors (DRs) can also directly impact immune cells and influence immune responses. Here, we review what is known about the role of TRAIL/DRs in immune cells and immune responses in general and in the tumor microenvironment in particular.
    Language English
    Publishing date 2019-09-30
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers11101469
    Database MEDical Literature Analysis and Retrieval System OnLINE

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