Nature Immunology
- 7, 954 - 961 (2006)
Published online: 6 August 2006; | doi:10.1038/ni1372
Inhibition of transcription factor NF- B in the central nervous system ameliorates autoimmune encephalomyelitis in miceGeert van Loo1, Rossana De Lorenzi1, Hauke Schmidt2, Marion Huth1, Alexander Mildner2, Marc Schmidt-Supprian3, Hans Lassmann4, Marco R Prinz2, 6 & Manolis Pasparakis1, 5, 61
European Molecular Biology Laboratory Mouse Biology Unit, I-00016 Monterotondo, Italy. 2
Department of Neuropathology, Georg August University, D-37075 Göttingen, Germany. 3
The CBR Institute for Biomedical Research, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA. 4
Brain Research Institute, University of Vienna, A-1090 Vienna, Austria. 5
Institute for Genetics, University of Cologne, D-50674 Cologne, Germany. 6
These authors contributed equally to this work.
Correspondence should be addressed to Manolis Pasparakis pasparakis@uni-koeln.de Activation of transcription factor NF- B in the central nervous system (CNS) has been linked to autoimmune demyelinating disease; however, it remains unclear whether its function is protective or pathogenic. Here we show that CNS-restricted ablation of 'upstream' NF-B activators NEMO or IKK2 but not IKK1 ameliorated disease pathology in a mouse model of multiple sclerosis, suggesting that 'canonical' NF-B activation in cells of the CNS has a mainly pathogenic function in autoimmune demyelinating disease. NF-B inhibition prevented the expression of proinflammatory cytokines, chemokines and the adhesion molecule VCAM-1 from CNS-resident cells. Thus, NF-B-dependent gene expression in non–microglial cells of the CNS provides a permissive proinflammatory milieu that is critical for CNS inflammation and tissue damage in autoimmune demyelinating disease.
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