Regulatory T Cells Promote Remyelination

Research Summary: Regulatory T cells promote myelin regeneration in the central nervous system

When we think about treating multiple sclerosis, generally there are two main approaches that are discussed.  Firstly, we can attempt to prevent damage from occurring.  This is the key concept behind all of the current therapies that exist – they suppress the immune system in a way designed to cease the attack on myelin.  Secondly, we could repair the damage that has been caused.  This concept is known as ‘remyelination’ and no currently approved treatments exist that work this way.  However, many new treatments in the pipeline are primarily focussed on fixing the scarred myelin.  In essence, a combination of both these approaches (stopping new damage and repairing existing damage) is likely to provide the best strategy in the foreseeable future.  Considering this, any new insights into how remyelination works are really important.

An international collaboration, led by researchers at Queen’s University Belfast, aimed to investigate the specific role that T cells might play in the myelin repair process.  Whilst T cells are known to cause damage to myelin, previous studies have also shown that they are also important for remyelination.  However, ‘T cells’ can relate to a wide range of different cell types, so finding the exact ones that are necessary for repair is important for our understanding.

Using a number of different approaches, the researchers were able to determine the following:

• A specific type of T cell, known as a regulatory T cell, is critical in the remyelination process in two different mouse models.

• These regulatory T cells were found to be present around the lesion site.  When they were depleted from the mice, the conversion of cells into oligodendrocytes (cells responsible for producing myelin) was decreased.  It could be increased again by re-injecting the regulatory T cells back into the mice.

• Using brain slices, the researchers were able to show that regulatory T cells had a specific impact on myelin production.  The results also indicated that it was something being secreted by the regulatory T cells that was having this effect.  It was found that this molecule was a growth protein known as CCN3.

• Regulatory T cells are known to play a role in modulating the immune system and so it was possible that they were helping myelin repair purely through reducing inflammation.  However, other experiments showed that the regulatory T cells still increased myelin production when inflammation was already low.

This research provides exceptionally strong evidence for the release of CCN3 by regulatory T cells to be important in myelin repair.  While it is performed in mouse models (and so will need to be confirmed to also be true in human studies), the fact that they have used two separate models and seen the same results is very encouraging.  Adding to that, the team employed a process to eliminate potential variables that might have provided other explanations for the results observed, which also strengthens the validity of their conclusions.

As mentioned earlier, this research is important for a couple of reasons.  Firstly, we know that many current therapies have an impact on suppressing the immune system.  This study shows that we should attempt to spare regulatory T cells when looking at treatments for MS, as they can actually have a significant beneficial effect on myelin repair.  Similarly, this is the first study that has shown CCN3 is important to stimulate the process of creating oligodendrocytes.  As oligodendrocytes are a hugely important cell type in remyelination, there is potential for CCN3 to be a novel treatment option for MS.  However, it is important to realise that this would still require lots of validation in human trials and, even if successful, be many years away from becoming widely available.

The abstract for this study can be read in full here.