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  1. Article ; Online: T-bet

    Rauch, Eileen / Amendt, Timm / Lopez Krol, Aleksandra / Lang, Fabian B / Linse, Vincent / Hohmann, Michelle / Keim, Ann-Christin / Kreutzer, Susanne / Kawengian, Kevin / Buchholz, Malte / Duschner, Philipp / Grauer, Saskia / Schnierle, Barbara / Ruhl, Andreas / Burtscher, Ingo / Dehnert, Sonja / Kuria, Chege / Kupke, Alexandra / Paul, Stephanie /
    Liehr, Thomas / Lechner, Marcus / Schnare, Markus / Kaufmann, Andreas / Huber, Magdalena / Winkler, Thomas H / Bauer, Stefan / Yu, Philipp

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 1229

    Abstract: Endogenous retroviruses (ERVs) are an integral part of the mammalian genome. The role of immune control of ERVs in general is poorly defined as is their function as anti-cancer immune targets or drivers of autoimmune disease. Here, we generate mouse- ... ...

    Abstract Endogenous retroviruses (ERVs) are an integral part of the mammalian genome. The role of immune control of ERVs in general is poorly defined as is their function as anti-cancer immune targets or drivers of autoimmune disease. Here, we generate mouse-strains where Moloney-Murine Leukemia Virus tagged with GFP (ERV-GFP) infected the mouse germline. This enables us to analyze the role of genetic, epigenetic and cell intrinsic restriction factors in ERV activation and control. We identify an autoreactive B cell response against the neo-self/ERV antigen GFP as a key mechanism of ERV control. Hallmarks of this response are spontaneous ERV-GFP
    MeSH term(s) Animals ; Mice ; Autoimmune Diseases/genetics ; B-Lymphocytes/immunology ; Endogenous Retroviruses/genetics ; Mammals/genetics
    Language English
    Publishing date 2024-02-09
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-024-45201-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Pro- and Antitumorigenic Capacity of Immunoproteasomes in Shaping the Tumor Microenvironment.

    Leister, Hanna / Luu, Maik / Staudenraus, Daniel / Lopez Krol, Aleksandra / Mollenkopf, Hans-Joachim / Sharma, Arjun / Schmerer, Nils / Schulte, Leon N / Bertrams, Wilhelm / Schmeck, Bernd / Bosmann, Markus / Steinhoff, Ulrich / Visekruna, Alexander

    Cancer immunology research

    2021  Volume 9, Issue 6, Page(s) 682–692

    Abstract: Apart from the constitutive proteasome, the immunoproteasome that comprises the three proteolytic subunits LMP2, MECL-1, and LMP7 is expressed in most immune cells. In this study, we describe opposing roles for immunoproteasomes in regulating the tumor ... ...

    Abstract Apart from the constitutive proteasome, the immunoproteasome that comprises the three proteolytic subunits LMP2, MECL-1, and LMP7 is expressed in most immune cells. In this study, we describe opposing roles for immunoproteasomes in regulating the tumor microenvironment (TME). During chronic inflammation, immunoproteasomes modulated the expression of protumorigenic cytokines and chemokines and enhanced infiltration of innate immune cells, thus triggering the onset of colitis-associated carcinogenesis (CAC) in wild-type mice. Consequently, immunoproteasome-deficient animals (LMP2/MECL-1/LMP7-null mice) were almost completely resistant to CAC development. In patients with ulcerative colitis with high risk for CAC, immunoproteasome-induced protumorigenic mediators were upregulated. In melanoma tumors, the role of immunoproteasomes is relatively unknown. We found that high expression of immunoproteasomes in human melanoma was associated with better prognosis. Similarly, our data revealed that the immunoproteasome has antitumorigenic activity in a mouse model of melanoma. The antitumor immunity against melanoma was compromised in immunoproteasome-deficient mice because of the impaired activity of CD8
    MeSH term(s) Animals ; Antineoplastic Agents/therapeutic use ; Cell Line, Tumor ; Colitis/pathology ; Cysteine Endopeptidases/deficiency ; Cysteine Endopeptidases/genetics ; Cysteine Endopeptidases/metabolism ; Cytokines/metabolism ; Female ; Histocompatibility Antigens Class I/metabolism ; Humans ; Melanoma, Experimental/drug therapy ; Melanoma, Experimental/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Proteasome Endopeptidase Complex/genetics ; Proteasome Endopeptidase Complex/metabolism ; T-Lymphocytes, Cytotoxic/immunology ; T-Lymphocytes, Cytotoxic/metabolism ; Tumor Microenvironment/immunology
    Chemical Substances Antineoplastic Agents ; Cytokines ; Histocompatibility Antigens Class I ; LMP-2 protein (144416-78-4) ; Cysteine Endopeptidases (EC 3.4.22.-) ; LMP7 protein (EC 3.4.25.1) ; Proteasome Endopeptidase Complex (EC 3.4.25.1)
    Language English
    Publishing date 2021-03-11
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2732489-8
    ISSN 2326-6074 ; 2326-6066
    ISSN (online) 2326-6074
    ISSN 2326-6066
    DOI 10.1158/2326-6066.CIR-20-0492
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 7022: Show issues Location:
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    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  3. Article ; Online: Lactate induces metabolic and epigenetic reprogramming of pro-inflammatory Th17 cells.

    Lopez Krol, Aleksandra / Nehring, Hannah P / Krause, Felix F / Wempe, Anne / Raifer, Hartmann / Nist, Andrea / Stiewe, Thorsten / Bertrams, Wilhelm / Schmeck, Bernd / Luu, Maik / Leister, Hanna / Chung, Ho-Ryun / Bauer, Uta-Maria / Adhikary, Till / Visekruna, Alexander

    EMBO reports

    2022  Volume 23, Issue 12, Page(s) e54685

    Abstract: Increased lactate levels in the tissue microenvironment are a well-known feature of chronic inflammation. However, the role of lactate in regulating T cell function remains controversial. Here, we demonstrate that extracellular lactate predominantly ... ...

    Abstract Increased lactate levels in the tissue microenvironment are a well-known feature of chronic inflammation. However, the role of lactate in regulating T cell function remains controversial. Here, we demonstrate that extracellular lactate predominantly induces deregulation of the Th17-specific gene expression program by modulating the metabolic and epigenetic status of Th17 cells. Following lactate treatment, Th17 cells significantly reduced their IL-17A production and upregulated Foxp3 expression through ROS-driven IL-2 secretion. Moreover, we observed increased levels of genome-wide histone H3K18 lactylation, a recently described marker for active chromatin in macrophages, in lactate-treated Th17 cells. In addition, we show that high lactate concentrations suppress Th17 pathogenicity during intestinal inflammation in mice. These results indicate that lactate is capable of reprogramming pro-inflammatory T cell phenotypes into regulatory T cells.
    MeSH term(s) Animals ; Mice ; Lactic Acid ; Th17 Cells ; Epigenomics
    Chemical Substances Lactic Acid (33X04XA5AT)
    Language English
    Publishing date 2022-10-10
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2020896-0
    ISSN 1469-3178 ; 1469-221X
    ISSN (online) 1469-3178
    ISSN 1469-221X
    DOI 10.15252/embr.202254685
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5433: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MG 41: Show issues

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