Inhibition of transcription factor NF-[kappa]B in the central nervous system ameliorates autoimmune encephalomyelitis in mice

Activation of transcription factor NF-kappaB 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-kappaB activators N...

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Veröffentlicht in:Nature Immunology 2006-09, Vol.7 (9), p.954-961
Hauptverfasser: Geert van Loo, De Lorenzi, Rossana, Schmidt, Hauke, Huth, Marion, Mildner, Alexander, Schmidt-Supprian, Marc, Lassmann, Hans, Prinz, Marco R, Pasparakis, Manolis
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container_end_page 961
container_issue 9
container_start_page 954
container_title Nature Immunology
container_volume 7
creator Geert van Loo
De Lorenzi, Rossana
Schmidt, Hauke
Huth, Marion
Mildner, Alexander
Schmidt-Supprian, Marc
Lassmann, Hans
Prinz, Marco R
Pasparakis, Manolis
description Activation of transcription factor NF-kappaB 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-kappaB activators NEMO or IKK2 but not IKK1 ameliorated disease pathology in a mouse model of multiple sclerosis, suggesting that 'canonical' NF-kappaB activation in cells of the CNS has a mainly pathogenic function in autoimmune demyelinating disease. NF-kappaB inhibition prevented the expression of proinflammatory cytokines, chemokines and the adhesion molecule VCAM-1 from CNS-resident cells. Thus, NF-kappaB-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.
doi_str_mv 10.1038/ni1372
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subjects Adhesion
Autoimmune diseases
Central nervous system
Pathology
title Inhibition of transcription factor NF-[kappa]B in the central nervous system ameliorates autoimmune encephalomyelitis in mice
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