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From The Scientist March Issue:

News:
Breaching the blood-brain barrier
Posted by Edyta Zielinska
[Entry posted at 23rd March 2009 04:21 PM GMT]
View comments(2) | Comment on this news story

Researchers have identified a novel mechanism by which immune cells wiggle their way across the blood-brain barrier in diseases such as multiple sclerosis (MS). A type of T-cell involved in autoimmune disease leads the way, entering the brain and perhaps priming the blood-brain barrier's membrane to attract other immune cells -- opening the door for those cells to do their inflammatory damage, according to a study published online yesterday (Mar 22) in Nature Immunology.

[SIZE=-2]The choroid plexus is a doorway
into the brain for T lymphocytes.

Image: Andrew Elston/
LifeSpan BioSciences, Inc.
[/SIZE]"This study certainly refines our understanding on how inflammatory cells cross the blood-brain barrier," said clinical immunologist Ralf Linker at St Josef-Hospital/Ruhr-University Bochum, who was not involved in the research.

The blood-brain barrier is a selectively permeable interface between brain tissue and circulating molecules and cells. For years, researchers studying MS have used a mouse model of the disease, experimental autoimmune encephalomyelitis (EAE), to try to untangle how immune cells make their way across the blood-brain barrier to initiate inflammation in the brain. Federica Sallusto at the Institute for Research in Biomedicine in Switzerland and her colleagues attacked the problem by looking at one likely candidate: a recently-discovered T-cell called Th-17 that plays an important role in mediating autoimmune diseases. Th-17's physiological mechanism is still unknown, and its role in MS inflammation has been controversial.

Sallusto and her team knocked out a receptor on Th-17's surface that helps direct its movement, and found that the knockout mice didn't develop EAE. The researchers also traced the path of Th-17 cells expressing the receptor, CCR6, in normal brains. CCR6's ligand, they observed, was highly expressed in an area of the brain called the choroid plexus -- suspected as an entry-point for inflammatory immune cells -- suggesting that the trafficking receptors lead Th-17 cells there.

Normal brains express CCR6's ligand, and Th-17 cells may even enter the brain as part of routine immuno-surveillance, Sallusto explained. In the study, Sallusto's group used Th-17 cells which had been exposed to a myelin protein to make them reactive against the myelin in brain tissue. Once the primed Th-17 cells entered the brain, they initiated an inflammatory response, recruiting other immune cells to cross the blood-brain barrier.

The researchers suspect that the Th-17 cell inflammatory reaction acts to weaken the blood-brain barrier by stimulating the surface of capillary epithelia to express adhesion molecules, the first step of immune cell entry from blood to tissue. Th-17 cells may also release cytokines, which attract other inflammatory cells to the area.

Patients with MS are generally treated with factors that block inflammatory cells from entering the brain, but many of these drugs dampen cells that are necessary for fighting normal infection and have numerous side-effects. If the CCR6 and its ligand work similarly in humans, blocking the process could inhibit the first stage of inflammation in MS, the researchers suggest. "Certainly, further functional studies on human Th-17 cells are necessary here," said Linker.

One caveat, said Sallusto, is that while such a strategy might help prevent recurring MS, in which the patient suffers flares or relapses of inflammation, it may not help patients with full blown MS, since CCR6's job is to facilitate initial access to the brain.
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Lily
 

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thanks Lily, very interesting :)
 

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Wow! Thanks Lily for posting this. I hope they find a way to transfer this information into actual medicine soon. It sounds like it could prevent, or at least slow disease in people where it is detected early:).
 
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