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"Guardian Molecule" May Lead to New MS Treatment

February 2, 2018

The interactions between testosterone and the immune system in male mice have been studied by scientists from Northwestern University in Chicago, IL. They have discovered a molecule that seems to protect against multiple sclerosis. The team of researchers had noted that this “guardian molecule” had eliminated MS symptoms in female mice. The findings have been said to possibly lead to an entirely new kind of therapy for the autoimmune disease.

Since women are more susceptible to MS, as well as other similar autoimmune diseases, the team explains that the differences in sex hormones are a “clear” influence. The development of MS in men, on the other hand, is closely linked to age-related decline in levels of testosterone, although the underlying cellular and molecular mechanisms are unclear.

Based on the mouse model of MS, researchers discovered that test0sterone prompts a group of immune cells called mast cells, which secrete a signaling molecule called interleukin 33 (IL-33) in males. IL-33, the “guardian molecule”, was found to trigger a series of chemical reactions that block the development of the Th17 immune cells which is what actually attacks the myelin sheath.

Without this protective IL-33 response, it was also found that the female MS mice showed damaging “Th17-dominant response, which can be reversed by IL-33 treatment.”

Melissa A Brown, professor of microbiology and immunology, continued to explain, “Because testosterone levels are seven to eight times lower in adult women compared to men, we speculate there are insufficient levels in females to activate this protective pathway. But we showed we can activate the pathway with the guardian molecule, IL-33." Researchers hope their findings will lead to new treatments for MS.

While most MS therapies that have been found to be extremely promising have broken new ground recently in suppressing the immune system, they can sometimes leave these patients feeling unwell and open to infection. Professor Brown explained that their findings have identified new and more specific molecular targets the immune intervention. This provides more hope in that this will lead to better therapies that leave most of the immune system intact. In addition to this, the team suggests that the pathway should be studied further in order to find out whether it is or is not involved in other autoimmune diseases that occur more often in women.