| Autor: |
Kalergis AM; Millennium Nucleus on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile. akalergis@bio.puc.cl/kalergis@vtr.net, Iruretagoyena MI, Barrientos MJ, González PA, Herrada AA, Leiva ED, Gutiérrez MA, Riedel CA, Bueno SM, Jacobelli SH |
| Jazyk: |
angličtina |
| Zdroj: |
Immunology [Immunology] 2009 Sep; Vol. 128 (1 Suppl), pp. e306-14. Date of Electronic Publication: 2008 Nov 07. |
| DOI: |
10.1111/j.1365-2567.2008.02964.x |
| Abstrakt: |
Autoimmune diseases, such as systemic lupus erythematosus (SLE), result from deficiencies in self-antigen tolerance processes, which require regulated dendritic cell (DC) function. In this study we evaluated the phenotype of DCs during the onset of SLE in a mouse model, in which deletion of the inhibitory receptor FcgammaRIIb leads to the production of anti-nuclear antibodies and glomerulonephritis. Splenic DCs from FcgammaRIIb-deficient mice suffering from SLE showed increased expression of co-stimulatory molecules. Furthermore, diseased mice showed an altered function of the nuclear factor-kappaB (NF-kappaB) transcription factor, which is involved in DC maturation. Compared with healthy animals, expression of the inhibitory molecule IkappaB-alpha was significantly decreased in mice suffering from SLE. Consistently, pharmacological inhibition of NF-kappaB activity in FcgammaRIIb-deficient mice led to reduced susceptibility to SLE and prevented symptoms, such as anti-nuclear antibodies and kidney damage. Our data suggest that the occurrence of SLE is significantly influenced by alterations of NF-kappaB function, which can be considered as a new therapeutic target for this disease. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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