Researchers ID a DNA-binding factor that may trigger MS

May 18, 2018
Researchers at the University of Geneva, Switzerland, and Geneva University Hospitals have identified a DNA-binding factor called TOX that might play a role in triggering multiple sclerosis. They found that TOX allows immune cells to cause autoimmune tissue destruction in the brain. The results of the research offer important insights into understanding and treatment of autoimmune diseases.

The study’s authors analyzed the infectious factors by studying the autoimmune reactions provoked by different pathogens. This was to pinpoint an element that might influence the development of MS where there has been an infection. The researchers selected two distinct pathogens that elicit a response from the immune system – one viral and one bacterial – that were then injected into healthy mice. They found an identical immune reaction from the lymphocytes called CD8+ T. However, only the mouse infected with the viral pathogen developed an inflammatory brain disease reminiscent to MS.

Based on these outcomes, the scientists analyzed how the expression of the genes in the CD8+ T cells varied according to the pathogen used to activate them. This helped them identify TOX, a DNA-binding factor expressed only in the cells activated by the viral pathogen. They found that the inflammation environment influences the expression of TOX in T lymphocytes, and that it could play a role in triggering the illness. The immunologists validated the link between TOX and MS in the experimental model by eliminating the expression of this DNA-binding factor in the CD8+ T lymphocytes of healthy mice. Although they received the viral pathogen, the mice did not develop the disease.

What, then, is the role of TOX in setting off multiple sclerosis? The brain has a limited regenerative capacity, which is why they have to protect themselves against the body's immune reactions, which can destroy its cells by wanting to fight the virus, creating irreversible damage. The brain then sets up barriers that block the passage of T lymphocytes. However, by altering the expression of some of the receptors on the surface of the CD8+ T lymphocytes responsible for receiving the blocking signals sent by the brain, TOX enables the cells to cross the safeguards and attack the brain cells, causing the outbreak of the disease. Following these analyses, the researchers noted that TOX was also expressed in T cells present in MS lesions. 

Results of mouse model studies sometimes do not translate to humans and may be years away from being a marketable treatment. However, the study’s authors said this is an encouraging result for understanding the causes of the disease but there is still lots of work to be done to ascertain what really causes MS in humans.

The study was published in the journal Immunity.

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