DNA-binding factor TOX might trigger MS
"Researchers at the University of Geneva (UNIGE), Switzerland, and Geneva University Hospitals (HUG) have identified a DNA-binding factor called TOX that might play a role in triggering multiple sclerosis. They found that TOX licenses immune cells to cause autoimmune tissue destruction in the brain.
The UNIGE researchers selected two distinct pathogens that elicit a response from the immune system, one viral and one bacterial, which were then injected into healthy mice. "We saw a quantitatively identical immune reaction from the lymphocytes called CD8+ T," says Nicolas Page, a researcher in UNIGE's Pathology and Immunology Department. "However, only the mouse infected with the viral pathogen developed an inflammatory brain disease reminiscent of multiple sclerosis."
Based on these outcomes, the scientists analysed 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. "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," continues Page.
What, then, is the role of TOX in setting off multiple sclerosis? "Our brains have a limited regenerative capacity," says Merkler, "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 UNIGE researchers noted that TOX was also expressed in T cells present in multiple sclerosis lesions."