Different types of immune cells gain access to nerve cells in the brain and spinal cord in different ways, according to multiple sclerosis (MS) researchers based at the University of Illinois in Chicago and the University of California, Irvine.
While it is known that two different kinds of immune cells, called Th1 and Th17, are involved in demyelination seen in MS, until now researchers didn't know how these cells crossed the blood-brain barrier to attack the myelin coating of nerve cells and cause MS.
The blood-brain barrier is a virtually impenetrable wall created by cells lining the interior surface of blood vessels which are bolted tightly together by proteins in what are called “tight junctions”. These tight junctions prevent certain chemicals and harmful microbes from gaining access to the brain and spine.
To explore how Th1 and Th17 immune cells cross the blood-brain barrier to gain access to the brain and spinal cord, the US researchers looked at the blood-brain barrier in mice with experimental autoimmune encephalomyelitis — the mouse version of MS.
The researchers genetically labelled the tight junctions in the mouse blood vessels to see what role they played in the mouse MS. The researchers noticed tight junctions were significantly deteriorated in the presence of Th17 cells, but noticed that Th1 cells did not pass through tight junctions like the Th17 cells did.
Instead, the Th1 cells got through the blood vessel walls using specialised cell structures called caveolae. These are small pits or "caves" found on cell surfaces which help the passage of various molecules into or through cells. In a group of mice with autoimmune encephalomyelitis (mouse MS) bred to lack caveolae, the researchers found almost no Th1 cells in the brain and spinal cord. They reasoned that Th1 cells pass through the blood-brain barrier using caveolae not through tight junctions like Th17 cells.
"This is the first time we have ever seen the different means by which these two cell types gain access to myelin and nerves," said Sarah Lutz, of the University of Illinois at Chicago "Now that we know how these cells get to neurons, drugs or small molecules can be designed that interfere with or block each of these processes to help treat and possibly prevent multiple sclerosis." She added. The study is published in the journal Cell Reports.