Wiede, Florian and Vana, Karen and Sedger, Lisa M. and Lechner, Anja and Koerner, Heinrich (2007) TNF-dependent overexpression of CCL21 is an underlying cause of progressive lymphoaccumulation in generalized lymphoproliferative disorder. EUROPEAN JOURNAL OF IMMUNOLOGY, 37 (2). pp. 351-357. ISSN 0014-2980,
Full text not available from this repository. (Request a copy)Abstract
The human condition autoimmune lymphoproliferative syndrome and the murine mutation generalized lymphoproliferative disorder (gld/gld) are both caused by mutations of Fas or Fas ligand and are characterized by severe splenomegaly and lymphadenopathy. In the mouse, the additional absence of TNF attenuates the gld/gld syndrome through an unknown mechanism. We hypothesized that this unexpected outcome was not mediated by increased apoptosis but changes of T cell localization. We demonstrated that the homeostatic chemokine CCL21 is strongly up-regulated in the spleen of C57BL/6 (B6).gld/gld and B6.gld/gld.TRAIL(-/-) mice. In contrast, a distinct consequence of TNF deficiency in B6.gld/gld mice was the substantially reduced splenic production of CCL21. An analysis of the cognate chemokine receptor CCR7 showed a complete, age-dependent down-regulation of this receptor on B6.gld/gld conventional peripheral T cells that are therefore unable to react to this chemokine. These results demonstrate a new role for the pro-inflammatory cytokine TNF and the TNF-regulated chemokine CCL21 in the complex etiology of the autoimmune syndrome in B6.gld/gld mice.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TUMOR-NECROSIS-FACTOR; CD4 T-CELLS; LPR MICE; CHEMOKINES; LIGAND; ALPHA; AUTOIMMUNITY; EXPRESSION; APOPTOSIS; DISEASE; autoimmunity; chemokine receptor; knockout mice; splenomegaly; T cells |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Immunologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Dec 2020 11:41 |
| Last Modified: | 22 Dec 2020 11:41 |
| URI: | https://pred.uni-regensburg.de/id/eprint/33209 |
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