TNF-dependent overexpression of CCL21 is an underlying cause of progressive lymphoaccumulation in generalized lymphoproliferative disorder

Wiede, Florian, Vana, Karen, Sedger, Lisa M, Lechner, Anja, and Korner, 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.

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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 ID: 1365
Item Type: Article (Refereed Research - C1)
Keywords: autoimmunity, chemokine receptor, knockout mice, splenomegaly, T cells
ISSN: 1521-4141
Date Deposited: 14 May 2007
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) > 920108 Immune System and Allergy @ 100%
Citation Count from Web of Science Web of Science 3
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