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Study: Innate lymphoid cells key to female MS susceptibility

6/1/2015

A novel discovery focusing on a type of white blood cell, the innate lymphoid cell, offers new insight into why women are more likely than men to develop multiple sclerosis. The research opens up new avenues for investigation into sex-determined disease susceptibility and could one day lead to better therapies for both men and women with MS.

Like most laboratories that study the mouse model of MS, female mice were used in almost all the research experiments. "When we induce the disease in this strain of female mice, virtually 100 percent of them get very sick," said Melissa Brown, lead author of the study and professor of microbiology-immunology at Northwestern University Feinberg School of Medicine. "Male mice either get no disease or very little, so MS researchers typically use females in their studies."

A graduate student was asked to run an experiment using two groups of female mice. One group was normal; the other had a genetic mutation in a growth factor receptor (c-kit) that prevented the development of a subset of immune cells. Previous experiments showed that female mice with the mutation didn't get as sick as normal mice, and researchers were looking into reasons why. However, instead of using females, the graduate student chose male littermates from each group.

"It was an honest mistake, but the results were striking; the male mice with the mutation got very, very sick," said Brown.

The research team realized that the mutation was behaving differently in males and females. They found that mice with the c-kit mutation lacked type 2 innate lymphoid cells. The researchers think that in males these cells produce a protein that may help to protect from the disease by interfering with the damaging immune response.

"We are now looking at what activates these cells preferentially in males and not in females. The next question is can we activate the innate lymphoid cells in females to decrease disease susceptibility?" Russi said.

Results of mouse model studies sometimes do not translate to humans and may be years away from being a marketable treatment. However, the authors’ findings could lead to a new approach to designing drug therapy that modulates, rather than suppressing, the immune system of MS patients, shifting the response to one that is not so damaging.

The findings were published in The Journal of Immunology.



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