The role of Th17 cells in blood-brain barrier disruption

[Kofi]

FASEB J. 2009 Nov 25

Cellular mechanisms of IL-17-induced blood-brain barrier disruption.
Huppert J, Closhen D, Croxford A, White R, Kulig P, Pietrowski E,
Bechmann I, Becher B, Luhmann HJ, Waisman A, Kuhlmann CR.
*Institute of Physiology and Pathophysiology andFirst Medical
Department, Johannes Gutenberg-University Mainz, Mainz,
Germany;Department of Pathology, Institute of Experimental Immunology,
University Hospital of Zurich, Zurich, Switzerland; andInstitute of
Anatomy, University of Leipzig, Leipzig, Germany.

Recently T-helper 17 (Th17) cells were demonstrated to disrupt the
blood-brain barrier (BBB) by the action of IL-17A. The aim of the
present study was to examine the mechanisms that underlie IL-17A-induced
BBB breakdown. Barrier integrity was analyzed in the murine brain
endothelial cell line bEnd.3 by measuring the electrical resistance
values using electrical call impedance sensing technology. Furthermore,
in-cell Western blots, fluorescence imaging, and monocyte adhesion and
transendothelial migration assays were performed. Experimental
autoimmune encephalomyelitis (EAE) was induced in C57BL/6 mice. IL-17A
induced NADPH oxidase- or xanthine oxidase-dependent reactive oxygen
species (ROS) production. The resulting oxidative stress activated the
endothelial contractile machinery, which was accompanied by a
down-regulation of the tight junction molecule occludin. Blocking either
ROS formation or myosin light chain phosphorylation or applying
IL-17A-neutralizing antibodies prevented IL-17A-induced BBB disruption.
Treatment of mice with EAE using ML-7, an inhibitor of the myosin light
chain kinase, resulted in less BBB disruption at the spinal cord and
less infiltration of lymphocytes via the BBB and subsequently reduced
the clinical characteristics of EAE. These observations indicate that
IL-17A accounts for a crucial step in the development of EAE by
impairing the integrity of the BBB, involving augmented production of
ROS.-Huppert, J., Closhen, D., Croxford, A., White, R., Kulig, P.,
Pietrowski, E., Bechmann, I., Becher, B., Luhmann, H. J., Waisman, A.,
Kuhlmann, C. R. W. Cellular mechanisms of IL-17-induced blood-brain
barrier disruption.

PMID: 19940258

[nightlight]

On Dec 5, 8:20 pm, Kofi <k...@anon.un> wrote:
>  FASEB J. 2009 Nov 25
>
>

> Recently T-helper 17 (Th17) cells were demonstrated to disrupt the
> blood-brain barrier (BBB) by the action of IL-17A. The aim of the
> present study was to examine the mechanisms that underlie IL-17A-induced
> BBB breakdown.

Coincidentally, nicotine suppresses Th17 activity:

"Activation of the Cholinergic Anti-Inflammatory System by
Nicotine Attenuates Neuroinflammation via Suppression of
Th1 and Th17 Responses"
[The Journal of Immunology, 2009]
http://www.jimmunol.org/cgi/content/abstract/jimmunol.0902212v1

The authors speculate that this may be the mechanism behind the
protective anti-inflammatory effects of tobacco smoke long known
from epidemiological observations. That is likely not the full
explanation since the full tobacco smoke results in more potent
protective anti-inflammatory effects than nicotine alone,
as demonstrated in recent experiments on mice:

"Smoking and nicotine exposure delay development of
collagen-induced arthritis in mice"

[Arthritis Research & Therapy 2009, 11:R88]
http://arthritis-research.com/content/11/3/R88