Immune cells play a role in endometriosis

UK scientists have discovered how cells in the immune system play a role in stimulating the growth and activity of nerve cells in endometriosis, leading to increased sensitivity to pain in the pelvic region. Their work has been published in The FASEB Journal.

Around 176 million women worldwide suffer from endometriosis, in which cells like the internal lining of the uterus (endometrium) grow outside of it in the form of lesions, typically in the pelvic (peritoneal) cavity. It can cause significant pelvic pain and is associated with infertility for some women with the condition. Treatment options are limited to surgical removal of lesions or medical management to suppress ovarian hormone production.

“Hormonal solutions rely on suppressing ovarian function but are not ideal as they can cause unwanted side effects, and prevent the user from becoming pregnant,” said lead author Dr Erin Greaves, from Warwick Medical School. “We are trying to find non-hormonal solutions.”

Collaborating with colleagues at the University of Warwick and the University of Edinburgh, Dr Greaves focused on the role of macrophages — white blood cells found in the immune system — in contributing to the pain caused by endometriosis. Previous studies have shown that macrophages can be involved in other types of chronic pain, but they have never before been linked to endometriosis. This is despite the fact that they are known to adapt their functions according to local signals and so become modified by disease, they are drawn to endometriosis lesions, and they are found in high numbers inside the lesions themselves.

Using a cell culture of these diseased-modified macrophages, the scientists observed increased production of the insulin-like growth factor-1 (IGF-1). Applying this onto nerve cells grown in culture, they found that this encouraged the nerves to grow and also activated them, demonstrating that production of IGF-1 by macrophages plays an important role in generating pain in endometriosis.

To further confirm their results, the researchers examined peritoneal fluid from women with endometriosis and found increased concentrations of IGF-1 compared to those without the condition. Those women also self-reported experiencing greater levels of pain.

Macrophages thus adopt a different gene expression in the presence of endometriosis lesions — and while this acts to increase the sensitivity to pain in that location, it may also act as a potential marker to target for treatment.

“If we can learn about the role of macrophages in endometriosis then we can distinguish them from healthy macrophages and target treatment to them,” Dr Greaves explained. “Macrophages are so crucial to our immune system tissue function and we need to know more about their roles, so this research goes some way in defining how macrophages are different in endometriosis.

“This discovery will go some way towards finding ways to relieve symptoms for women who suffer from endometriosis. We hope that in the future we can learn exactly how disease-modified macrophages in endometriosis promote disease and how we can target them in order to treat endometriosis.”

Image caption: Human sensory neurons derived from stem cells cultured in the lab. Image credit: Alexandra Sarginson.

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