Until now, there has been no recognised pathway for immune cells to travel through the brain to carry out routine ‘surveillance’ to protect against autoimmune attack. Associate Professor Brown has identified a specific pathway along which immune cells called dendritic cells travel, to reach the lymph nodes in the neck. Once inside the lymph nodes, dendritic cells communicate with inflammatory immune T cells – essentially teaching the T cells not to attack proteins in the brain.
Associate Professor Brown and his team mapped the dendritic cell pathway and demonstrated that blocking the pathway enhanced MS-like disease in the mice.
While it is already known that blocking the entry of T cells into the brain can reduce MS disease activity, this is the first time that it has been demonstrated that blocking ‘helpful’ immune cells from leaving the brain might increase disease activity.
This is crucial information as certain MS drugs, such as fingolimod, act by blocking the traffic of inflammatory immune cells into the brain. This work suggests that MS treatments could be more effective, with fewer side effects, if they only acted on immune cells coming into the brain. One way to do this, which is already under investigation by Associate Professor Brown, would be to deliver the drugs to lymph nodes in the neck. This method of drug delivery would reduce unwanted side effects and increase therapeutic effects.
While this research was undertaken in animal models, it is thought that a similar pathway may exist in the human brain.
‘This work is the first to identify this pathway of immune cell traffic through the brain’, commented Associate Professor Brown, ‘and means we need to markedly revise our understanding of the intercommunication between the immune system and the brain and what goes awry in MS’.
‘This is an outstanding example of the kind of basic research funded by MS Research Australia that can lead to true changes in our understanding of the way the healthy brain functions and what might be going wrong in MS,’ said Dr Matthew Miles, Chief Executive Officer of MS Research Australia, ‘We congratulate Associate Professor David Brown on this great research’.
To read the abstract please see here