Both Tumor Necrosis Factor Receptor Signaling Pathways Contribute to Mortality but not to Splenomegaly in Generalized Lymphoproliferative Disorder
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 an...
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| Format: | Article |
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MDPI AG
2014-12-01
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| Series: | Antibodies |
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| Online Access: | http://www.mdpi.com/2073-4468/4/1/1 |
| _version_ | 1828967299903651840 |
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| author | Florian Wiede Alicia Roomberg Jocelyn Darby Rene Gollan Heinrich Körner |
| author_facet | Florian Wiede Alicia Roomberg Jocelyn Darby Rene Gollan Heinrich Körner |
| author_sort | Florian Wiede |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T11:47:25Z |
| format | Article |
| id | doaj.art-cc348d6e37d6467197cb59e03bab5841 |
| institution | Directory Open Access Journal |
| issn | 2073-4468 |
| language | English |
| last_indexed | 2024-12-14T11:47:25Z |
| publishDate | 2014-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibodies |
| spelling | doaj.art-cc348d6e37d6467197cb59e03bab58412022-12-21T23:02:30ZengMDPI AGAntibodies2073-44682014-12-014111010.3390/antib4010001antib4010001Both Tumor Necrosis Factor Receptor Signaling Pathways Contribute to Mortality but not to Splenomegaly in Generalized Lymphoproliferative DisorderFlorian Wiede0Alicia Roomberg1Jocelyn Darby2Rene Gollan3Heinrich Körner4Comparative Genomics Centre, James Cook University, Townsville, Qld 4811, AustraliaComparative Genomics Centre, James Cook University, Townsville, Qld 4811, AustraliaHeinrich Körner, Menzies Research Institute Tasmania, Medical Science 2, 17 Liverpool Street, Hobart, Tasmania 7000, AustraliaComparative Genomics Centre, James Cook University, Townsville, Qld 4811, AustraliaHeinrich Körner, Menzies Research Institute Tasmania, Medical Science 2, 17 Liverpool Street, Hobart, Tasmania 7000, AustraliaThe 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.http://www.mdpi.com/2073-4468/4/1/1autoimmunitytumor necrosis factortumor necrosis factor receptorgene-deficient models |
| spellingShingle | Florian Wiede Alicia Roomberg Jocelyn Darby Rene Gollan Heinrich Körner Both Tumor Necrosis Factor Receptor Signaling Pathways Contribute to Mortality but not to Splenomegaly in Generalized Lymphoproliferative Disorder Antibodies autoimmunity tumor necrosis factor tumor necrosis factor receptor gene-deficient models |
| title | Both Tumor Necrosis Factor Receptor Signaling Pathways Contribute to Mortality but not to Splenomegaly in Generalized Lymphoproliferative Disorder |
| title_full | Both Tumor Necrosis Factor Receptor Signaling Pathways Contribute to Mortality but not to Splenomegaly in Generalized Lymphoproliferative Disorder |
| title_fullStr | Both Tumor Necrosis Factor Receptor Signaling Pathways Contribute to Mortality but not to Splenomegaly in Generalized Lymphoproliferative Disorder |
| title_full_unstemmed | Both Tumor Necrosis Factor Receptor Signaling Pathways Contribute to Mortality but not to Splenomegaly in Generalized Lymphoproliferative Disorder |
| title_short | Both Tumor Necrosis Factor Receptor Signaling Pathways Contribute to Mortality but not to Splenomegaly in Generalized Lymphoproliferative Disorder |
| title_sort | both tumor necrosis factor receptor signaling pathways contribute to mortality but not to splenomegaly in generalized lymphoproliferative disorder |
| topic | autoimmunity tumor necrosis factor tumor necrosis factor receptor gene-deficient models |
| url | http://www.mdpi.com/2073-4468/4/1/1 |
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