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    ‘Guardian molecule’ that protects men from MS identified

    1 February 2018

    Men are significantly less likely to get multiple sclerosis than women, because they are protected by high levels of testosterone.

    According to new research published in the Proceedings of the National Academy of Sciences, we are a step closer to understanding how that protective mechanism works.

    Using a mouse model of MS, the researchers identified a guardian molecule – triggered by testosterone – that appears to protect males from the disease.

    When female mice with MS are treated with this protective molecule, their symptoms were eliminated.

    The study’s lead author, Melissa Brown, said: ‘This suggests a mechanism for the reduced incidence of multiple sclerosis and other autoimmune diseases in males compared to females.’

    ‘These findings could lead to an entirely new kind of therapy for MS, which we greatly need.’

    Until now, scientists haven’t understood how the testosterone provides protection from MS.

    The discovery stemmed from an accident in the lab in which male mice were used instead of female mice, because a graduate student hadn’t yet learned to identify the almost imperceptible genitals of male mouse pups.

    The researchers, from Northwestern University in the US, demonstrated that testosterone causes mast cells, a type of immune cell, to produce the so-called guardian molecule, cytokine IL-33, in male mice.

    The guardian molecule triggers a cascade of chemicals that prevents the development of another type of immune cell (Th17 cells) that can directly attack myelin.

    In this model of disease, similar to MS in humans, females develop more of a disease-causing Th17 immune response than males. These Th17 cells, attack and destroy myelin. But that damaging response was reversed in females by treatment with IL-33.

    Brown said: ‘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.’

    ‘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. This testosterone-driven protective pathway should also be studied in other female-biased autoimmune diseases.’