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

Citation

Wiede, F and Roomberg, A and Darby, J and Gollan, R and Korner, H, Both Tumor Necrosis Factor Receptor Signaling Pathways Contribute to Mortality but not to Splenomegaly in Generalized Lymphoproliferative Disorder, Antibodies, 4, (1) pp. 1-10. ISSN 2073-4468 (2015) [Refereed Article]


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Copyright 2014 The Author Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) License http://creativecommons.org/licenses/by/4.0/

DOI: doi:10.3390/antib4010001

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 Details

Item Type:Refereed Article
Keywords:TNFR
Research Division:Medical and Health Sciences
Research Group:Immunology
Research Field:Autoimmunity
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Immune System and Allergy
Author:Darby, J (Ms Jocelyn Darby)
Author:Korner, H (Professor Heinrich Korner)
ID Code:97579
Year Published:2015 (online first 2014)
Funding Support:National Health and Medical Research Council (485807)
Deposited By:Menzies Institute for Medical Research
Deposited On:2014-12-23
Last Modified:2015-04-22
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