Both tumor necrosis factor receptor signaling pathways contribute to mortality but not to splenomegaly in generalized lymphoproliferative disorder

Wiede, Florian, Roomberg, Alicia, Darby, Jocelyn, Gollan, Rene, and Körner, Heinrich (2015) Both tumor necrosis factor receptor signaling pathways contribute to mortality but not to splenomegaly in generalized lymphoproliferative disorder. Antibodies, 4 (1). pp. 1-10.

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Abstract

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 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.

Item ID: 44061
Item Type: Article (Research - C1)
ISSN: 2073-4468
Keywords: tumor necrosis factor, gene-deficient models, tumor necrosis factor receptor, autoimmunity
Additional Information:

This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Funders: National Health and Medical Research Council of Australia (NHMRC)
Date Deposited: 06 Apr 2016 07:41
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110704 Cellular Immunology @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920199 Clinical Health (Organs, Diseases and Abnormal Conditions) not elsewhere classified @ 100%
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