A new Japanese study, published recently in the journal Nature Communications, may provide important clues about how and why certain immune system cells behave differently in MS.
In MS, the immune system mistakenly attacks the cells of the brain and spinal cord in a process known as autoimmunity. Identifying the precise way in which immune cells carry out this attack is important, since it could provide researchers with new targets that are able to block or change the autoimmune process.
There are two ways that the immune system response is different in MS. The first is that the T helper immune cells (known as Th1 and Th17), which normally respond to the presence of an infection in the body, begin to attack healthy cells. The second is that another type of immune cell, known as regulatory T cells, which normally suppress the actions of the T helper cells, are different in people with MS. The regulatory T cells are fewer in number and do not work as well in MS. However, exactly how and why regulatory T cells are lower and behave differently in MS is not clear.
In this new study, researchers from the National Center of Neurology and Psychiatry in Japan have examined the role of specific molecules – microRNAs – in MS. MicroRNAs are short sections of RNA, a DNA-like material which regulates the activity of genes within cells. They can act as gene switches, telling cells whether or not to use specific genes at any given time. Cells can excrete microRNAs in small packages known as exosomes, as a method of communication between cells.
The researchers looked at the circulating exosomes in the blood of people with MS and compared these with samples taken from people without MS. They found that the exosomes taken from people with MS reduced the growth of regulatory T cells in a dish in the laboratory, whereas exosomes from people without MS had no effect.
It was likely that the action of the exosomes on regulatory T cells was due to the microRNAs contained within the exosomes. So, the researchers then profiled the microRNAs contained within the exosomes. They identified that the microRNAs contained within the exosomes of people with MS were very different from those without MS.
In particular, one microRNA seemed to be responsible for reducing the growth of the regulatory T cells. This microRNA, called “let-7i”, was significantly more abundant in the exosomes from people with MS. When this microRNA was added directly to regulatory T cells in a laboratory dish, growth of the cells was slowed. Importantly, when more of this microRNA was added or the microRNA itself was blocked, growth of the cells was correspondingly reduced or increased.
The researchers were also able to show that the let-7i microRNA acts as a genetic switch for two molecules in immune cells, both of which control the development of regulatory T cells in the immune system.
This important work has identified that the let-7i microRNA, as well as these two molecules, act together to set up the differences seen in regulatory T cells in MS – one of the key autoimmune processes that leads to MS.
This work offers valuable insights into an important mechanism that helps to keep autoimmune cells in check and how this mechanism can function incorrectly in MS.
With thanks to MS Research Australia – the lead provider of research summaries on our website.