Both Tumor Necrosis Factor Receptor Signaling Pathways Contribute to Mortality but not to Splenomegaly in Generalized Lymphoproliferative Disorder

نویسندگان

  • Florian Wiede
  • Alicia Roomberg
  • Jocelyn Darby
  • Rene Gollan
  • Dimiter S. Dimitrov
چکیده

The phenotypical consequences of a combined deficiency of the Fas-Fas Ligand (FasL) and one or both Tumor Necrosis Factor (TNF) signaling pathways were investigated. Mice, which expressed a non-functional FasL suffered from a pathological accumulation of both B and T cells leading to splenomegaly and lymphadenopathy and, depending on the genetic background, pathogenic self-reactive antibodies (generalized lymphoproliferative disorder (gld)-phenotype). If mice additionally lacked TNF, they displayed a significantly ameliorated gld-phenotype while TNF Receptor-1-deficient gld mice (B6.gld.TNFR1) displayed a more severe phenotype. To complement this combination, we also generated TNF Receptor-2-deficient gld mice (B6.gld.TNFR2). Both double knockouts followed in their splenic structure the respective TNFR contribution to the phenotype. TNFR1 mice showed an absence of B cell follicles in the spleen while TNFR2 mice were comparable OPEN ACCESS Antibodies 2015, 4 2 to WT mice. In general, we demonstrated a strong contribution of both TNFR signaling pathways to the symptoms of gld with the notable exception of splenomegaly where only TNFR1 played a role.

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تاریخ انتشار 2014