Epigenetics: Switching genes on and off in MS

Australian researchers are deciphering the epigenetic changes in the immune systems of people with MS.

Researchers at the Hunter Medical Research Institute in NSW, funded by MS Research Australia, have published new research revealing how epigenetic changes may be important in MS.

  • Epigenetics are a set of instructions that tell cells how to read DNA.
  • Australian researchers have revealed epigenetic changes in people with MS.
  • These epigenetic changes were specific to certain cells in the immune system.

But to understand the potential impact of this study on MS we first need a crash course in epigenetics. Epigenetics may sound complex, but it is a simple way for cells to control genes. Epigenetics are a set of instructions, or chemical tags, in addition to the actual code of the DNA sequence, that help control whether genes are switched on or off, in any particular cell. A very visual example of this is the epigenetic tags that control the production of pigments only in certain skin cells to make the zebra’s stripes and the Dalmatian’s spots. These same switches of course exist in humans too and can control much more subtle and complex cell functions, such as how immune cells work.

Researchers from the Hunter Medical Research Institute, several of whom have been recipients of MS Research Australia grants including Dr Vicki Maltby, Dr Rod Lea and Associate Professor Jeannette Lechner-Scott, are world-class experts in this area.

In one study, they have collaborated with a number of international scientists to look in detail at the epigenetic changes in different types of T cells of the immune system, which are believed to have an important role in MS – the CD4 and CD8 T cells. In this study of T cells recently published in the scientific journal PLOS One the team looked at the cells purified from the blood of a group of Norwegian and Australian people with and without MS, and used the latest technologies to examine the DNA for the epigenetic tags, known as methyl groups, or methylation. With close to 100 people with MS in this study, it represents the largest study to date on the role of DNA methylation of immune cells in people with MS.

In a separate study, published in the prestigious journal Scientific Reports, the Hunter Medical Research Institute team also examined the epigenetic changes in the B cells of 24 people with relapsing remitting MS and compared it to 24 people without MS.

Together these studies highlight the importance of looking at individual cell populations in the immune system for the genetic and epigenetic changes that may influence MS. They found that both CD4 and CD8 T cells had a higher degree of methylation compared to those without MS, however the difference in the CD8 T cells was much more profound. On the other hand, B cells had fewer areas of methylation in people with MS.

When the researchers looked in close detail at where these epigenetic tags were found, they identified some particular regions of DNA in T cells, which were tagged differently in people with MS. One was the HLA-DRB1 gene which is the single gene that has been mostly strongly linked to the development of MS. Another gene known as SLFN12 is known to respond to changes in the activity of the immune system. In B cells they identified that several MS-associated genes, known as SLC44A2, LTBR, CARD11 and CXCR5 were tagged differently in people with MS.

These findings suggest that in MS, different immune cells have different genes switched on and off. More work will be needed to untangle the complex immune cell interactions and functions that are influenced by these epigenetic tags, but it is likely that they may influence the risk of developing MS, disease course in MS or response to therapy.

While not directly tested in this study, it is known that a number of the environmental risk factors for MS, such as smoking, obesity, vitamin D deficiency and Epstein Barr Virus (EBV) can all affect the epigenetics of cells. So this work may ultimately help explain how our genes and our environmental exposures contribute to the risk of getting MS as well as the great variation in how MS affects individuals – just like the pigments being switched on and off in the skin of a zebra creating a unique pattern!

But understanding how these patterns emerge is absolutely key to developing an individual, personalised approach to treating and managing MS.

Rohan Greenland The May 50K

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Epigenetics: Switching genes on and off in MS