In a new Northwestern University study, scientists have found a "guardian" molecule that is triggered by testosterone that appears to protect males from multiple sclerosis (MS). The work was published today in the Proceedings of the National Academy of Sciences.
The origin of the study originated from a mistake that a graduate student made. This graduate student had not learned how to identify the differences between male and female pups. Due to their mistake, they used male mice by accident, but that mistake led to a fascinating discovery.
In this study, the team showed that testosterone caused mast cells to produce IL-33 in male mice. IL-33 then triggers a cascade to prevent the development of Th17 cells, which can attack the myelin and cause MS.
In this disease model, similar to MS in humans, females develop more of a disease-causing Th17 immune response than males. However, that can be reversed in females if treated with IL-33.
"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," said lead study author Melissa Brown. "But we showed we can activate the pathway with the guardian molecule, IL-33."
The researchers also found that women tend to develop MS at a younger age and have a relapsing-remitting course of the disease. On the other hand, men tend to develop the disease later in life and it usually worsens without a period of improvement. The timing of the disease development in men also correlates with age-related reduction of testosterone levels.
"Our findings have identified new and more specific cellular and molecular targets for immune intervention that we hope will lead to better therapies that leave most of the immune system intact," Brown said. "This testosterone-driven protective pathway should also be studied in other female-biased autoimmune diseases."