title: Cellular-FLIP, Raji isoform (c-FLIP R) modulates cell death induction upon T-cell activation and infection.
abstract: 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.
authors.affiliation: Laboratory of Systems-Oriented Immunology and Inflammation Research, Institute of Molecular and Clinical Immunology, Otto-von-Guericke-University, Magdeburg, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Telieps
authors.forename: Frida
authors.initials: F
authors.lastname: Ewald
authors.forename: Marcus
authors.initials: M
authors.lastname: Gereke
authors.forename: Michaela
authors.initials: M
authors.lastname: Annemann
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Rauter
authors.forename: Marc
authors.initials: M
authors.lastname: Schuster
authors.forename: Nana
authors.initials: N
authors.lastname: Ueffing
authors.forename: Dorthe
authors.initials: D
authors.lastname: von Smolinski
authors.forename: Achim D
authors.initials: AD
authors.lastname: Gruber
authors.forename: Dunja
authors.initials: D
authors.lastname: Bruder
authors.forename: Ingo
authors.initials: I
authors.lastname: Schmitz
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000276:immunology; D057809:HEK293 Cells; D006801:Humans; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology*; D008099:Liver / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009336:Necrosis / Q000235:genetics / Q000276:immunology; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*; D019014:fas Receptor / Q000378:metabolism
chemical_list: D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D020033:Protein Isoforms; D019014:fas Receptor