Cellular‐FLIP, Raji isoform (c‐FLIPR) modulates cell death induction upon T‐cell activation and infection. Issue 6 (2nd May 2013)

• Record Type: Journal Article
• Authors: Telieps, Tanja; Ewald, Frida; Gereke, Marcus; Annemann, Michaela; Rauter, Yvonne; Schuster, Marc; Ueffing, Nana; von Smolinski, Dorthe; Gruber, Achim D.; Bruder, Dunja; Schmitz, Ingo
• Is Part Of: European journal of immunology. Volume 43:Issue 6(2013:Jun.)
• Page Start: 1499
• Page End: 1510
• Publication Date: 2013-05-02
• Subjects: Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201242819
• Languages: English
• ISSNs: 0014-2980

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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‐FLIP<sub>L</sub> and c‐FLIP<sub>S</sub> are well characterized, the function of c‐FLIP<sub>R</sub> remains poorly understood. Here, we demonstrate the induction of endogenous murine c‐FLIP<sub>R</sub> in activated lymphocytes for the first time. To analyze c‐FLIP<sub>R</sub> function in vivo<italic>, </italic> we generated transgenic mice expressing murine c‐FLIP<sub>R</sub> specifically in hematopoietic cells. As expected, lymphocytes from c‐FLIP<sub>R</sub> 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 <italic>Listeria monocytogenes</italic>, c‐FLIP<sub>R</sub> transgenic mice showed less liver necrosis and better bacterial clearance compared with infected wild‐type mice. We conclude that c‐FLIP<sub>R</sub> expression in hematopoietic cells supports an efficient immune response against bacterial infections.</p> </abstract>