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    Cellular-FLIP, Raji Isoform (c-FLIP R) Modulates Cell Death Induction upon T-Cell Activation and Infection (2013)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Telieps, Tanja
    Ewald, Frida
    Gereke, Marcus
    Annemann, Michaela
    Rauter, Yvonne
    Schuster, Marc
    Ueffing, Nana
    von Smolinski, Dorthe (WE 12)
    Gruber, Achim D (WE 12)
    Bruder, Dunja
    Schmitz, Ingo
    Quelle
    European journal of immunology : basic, clinical, translational
    Bandzählung: 43
    Heftzählung: 6
    Seiten: 1499 – 1510
    ISSN: 1521-4141
    Sprache
    Englisch
    Verweise
    DOI: 10.1002/eji.201242819
    Pubmed: 23505065
    Kontakt
    Institut für Tierpathologie

    Robert-von-Ostertag-Str. 15
    14163 Berlin
    +49 30 838 62450
    pathologie@vetmed.fu-berlin.de

    Abstract / Zusammenfassung

    Dysregulation of apoptosis caused by an imbalance of pro- and anti-apoptotic protein expression can lead to cancer, neurodegenerative, and autoimmune diseases. Cellular-FLIP (c-FLIP) proteins inhibit apoptosis directly at the death-inducing signaling complex of death receptors, such as CD95, and have been linked to apoptosis regulation during immune responses. While the isoforms c-FLIPL and c-FLIPS are well characterized, the function of c-FLIPR remains poorly understood. Here, we demonstrate the induction of endogenous murine c-FLIPR in activated lymphocytes for the first time. To analyze c-FLIPR function in vivo, we generated transgenic mice expressing murine c-FLIPR specifically in hematopoietic cells. As expected, lymphocytes from c-FLIPR transgenic mice were protected against CD95-induced apoptosis in vitro. In the steady state, transgenic mice had normal cell numbers and unaltered frequencies of B cells and T-cell subsets in lymphoid organs. However, when challenged with Listeria monocytogenes, c-FLIPR transgenic mice showed less liver necrosis and better bacterial clearance compared with infected wild-type mice. We conclude that c-FLIPR expression in hematopoietic cells supports an efficient immune response against bacterial infections.