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dc.contributor.authorEwald, F
dc.contributor.authorAnnemann, M
dc.contributor.authorPils, M C
dc.contributor.authorPlaza-Sirvent, C
dc.contributor.authorNeff, F
dc.contributor.authorErck, C
dc.contributor.authorReinhold, D
dc.contributor.authorSchmitz, I
dc.date.accessioned2014-05-16T15:02:40Z
dc.date.available2014-05-16T15:02:40Z
dc.date.issued2014
dc.identifier.citationConstitutive expression of murine c-FLIPR causes autoimmunity in aged mice. 2014, 5:e1168 Cell Death Disen
dc.identifier.issn2041-4889
dc.identifier.pmid24722293
dc.identifier.doi10.1038/cddis.2014.138
dc.identifier.urihttp://hdl.handle.net/10033/317064
dc.description.abstractDeath 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.
dc.language.isoenen
dc.rightsArchived with thanks to Cell death & diseaseen
dc.titleConstitutive expression of murine c-FLIPR causes autoimmunity in aged mice.en
dc.typeArticleen
dc.identifier.journalCell death & diseaseen
refterms.dateFOA2018-06-12T23:42:21Z
html.description.abstractDeath 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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