Publikationsdatenbank

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; 43(6) — S. 1499–1510

ISSN: 1521-4141

Sprache

Englisch

Verweise

DOI: 10.1002/eji.201242819

Pubmed: 23505065

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
Gebäude 12
14163 Berlin
+49 30 838 62450

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.