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Ewald, F.* ; Annemann, M.* ; Pils, M.C.* ; Plaza-Sirvent, C.* ; Neff, F. ; Erck, C.* ; Reinhold, D.* ; Schmitz, I.*

Constitutive expression of murine c-FLIPR causes autoimmunity in aged mice.

Cell Death Dis. 5:e1168 (2014)
Verlagsversion Volltext DOI PMC
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Death receptor-mediated apoptosis is a key mechanism for the control of immune responses and dysregulation of this pathway may lead to autoimmunity. Cellular FLICE-inhibitory proteins (c-FLIPs) are known as inhibitors of death receptor-mediated apoptosis. The only short murine c-FLIP splice variant is c-FLIPRaji (c-FLIPR). To investigate the functional role of c-FLIPR in the immune system, we used the vavFLIPR mouse model constitutively expressing murine c-FLIPR in all hematopoietic compartments. Lymphocytes from these mice are protected against CD95-mediated apoptosis and activation-induced cell death. Young vavFLIPR mice display normal lymphocyte compartments, but the lymphocyte populations alter with age. We identified reduced levels of T cells and slightly higher levels of B cells in 1-year-old vavFLIPR mice compared with wild-type (WT) littermates. Moreover, both B and T cells from aged vavFLIPR animals show activated phenotypes. Sera from 1-year-old WT and transgenic animals were analysed for anti-nuclear antibodies. Notably, elevated titres of these autoantibodies were detected in vavFLIPR sera. Furthermore, tissue damage in kidneys and lungs from aged vavFLIPR animals was observed, indicating that vavFLIPR mice develop a systemic lupus erythematosus-like phenotype with age. Taken together, these data suggest that c-FLIPR is an important modulator of apoptosis and enforced expression leads to autoimmunity.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter C-flip ; Apoptosis ; Cd95 ; Autoimmunity; Regulatory T-cells; Flice-inhibitory Protein; Caspase-8 Activation; Multiple-sclerosis; Signaling Complex; Cellular-flip; Systemic Autoimmunity; Mediated Apoptosis; Up-regulation; Death
Sprache englisch
Veröffentlichungsjahr 2014
HGF-Berichtsjahr 2014
ISSN (print) / ISBN 2041-4889
e-ISSN 2041-4889
Zeitschrift Cell Death & Disease
Quellenangaben Band: 5, Heft: 4, Seiten: , Artikelnummer: e1168 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Pathology (PATH)
POF Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Forschungsfeld(er) Enabling and Novel Technologies
PSP-Element(e) G-500300-001
PubMed ID 24722293
DOI 10.1038/cddis.2014.138
WOS ID WOS:000335450400014
Scopus ID 84901068274
Erfassungsdatum 2014-04-30
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