Researchers cause a lupus-like disease in mice by amplifying the amount of a single “master regulator” factor — suggesting both a root cause for known differences between the sexes and a target for new treatments.

It’s one of the great mysteries of medicine, and one that affects the lives of millions of people: Why do women’s immune systems gang up on them far more than men’s do, causing far more women to develop autoimmune diseases such as lupus?

Part of the answer, it turns out, may lie in the skin.

New evidence points to a key role for a molecular switch called VGLL3. Three years ago, a team of University of Michigan researchers showed that women have more VGLL3 in their skin cells than men do.

Now, working in mice, they’ve discovered that having too much VGLL3 in skin cells pushes the immune system into overdrive, leading to a “self-attacking” autoimmune response. Surprisingly, this response extends beyond the skin, attacking internal organs, too.

 

Credit: CDC

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