Potential Multiple Sclerosis Trigger Identified

Researchers have identified a potential trigger of multiple sclerosis (MS), moving a step closer to a better understanding of the disease, according to a study recently published in Immunity.

In the study, researchers used an experimental mouse model to pinpoint what might influence the development of MS through infectious factors. Although it is known that both genetic and environmental risk factors come into play, it remains a mystery as to why MS can be triggered in some cases but not others.

Researchers at the University of Geneva (UNIGE), Switzerland, and Geneva University Hospital used 2 distinct pathogens—one viral and one bacterial—that elicit an immune system response and injected them into healthy mice.

According to the researchers, they observed an identical immune reaction from the lymphocytes called CD8+ T in the infected mice. However, only the mice infected with a viral pathogen developed an inflammatory brain disease reminiscent to MS, the study authors noted.

Next, the researchers identified TOX, a DNA-binding factor expressed only in the cells activated by the viral pathogen. To determine the role of TOX in MS development, the researchers eliminated TOX expression in the CD8+ T lymphocytes of healthy mice and then injected them with the viral pathogen. These mice did not develop MS.

“We found that the inflammation environment influences the expression of TOX in T lymphocytes, and that it could play a role in triggering the illness,” Nicolas Page, a researcher in UNIGE’s pathology and immunology department, said in a press release.

According to the researchers, the brain protects itself against the body’s immune reactions by creating barriers to block the passage of T lymphocytes. TOX alters 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, enabling the cells to cross the safeguards and attack the brain cells.

The researchers added that TOX was also expressed in T cells present in MS lesions.

“This is an encouraging result for understanding the causes of the disease but there is still a lot of work to be done to ascertain what really causes multiple sclerosis in humans,” Page concluded.

Reference

Page N, Klimek B, De Roo M, et al. Expression of the DNA-Binding Factor TOX Promotes the Encephalitogenic Potential of Microbe-Induced Autoreactive CD8⁺ T Cells. Immunity. 2018. Doi: https://doi.org/10.1016/j.immuni.2018.04.005