Cellular-FLIP, Raji isoform (c-FLIP R) modulates cell death induction upon T-cell activation and infection

Autor: Tanja, Telieps, Frida, Ewald, Marcus, Gereke, Michaela, Annemann, Yvonne, Rauter, Marc, Schuster, Nana, Ueffing, Dorthe, von Smolinski, Achim D, Gruber, Dunja, Bruder, Ingo, Schmitz
Rok vydání: 2012
Předmět:
Zdroj: European journal of immunology. 43(6)
ISSN: 1521-4141
Popis: 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.
Databáze: OpenAIRE