| First Author | Wiede F | Year | 2007 |
| Journal | Eur J Immunol | Volume | 37 |
| Issue | 2 | Pages | 351-7 |
| PubMed ID | 17236235 | Mgi Jnum | J:117875 |
| Mgi Id | MGI:3697942 | Doi | 10.1002/eji.200636218 |
| Citation | Wiede F, et al. (2007) TNF-dependent overexpression of CCL21 is an underlying cause of progressive lymphoaccumulation in generalized lymphoproliferative disorder. Eur J Immunol 37(2):351-7 |
| abstractText | 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. |
