Potential New Target to Treat Endometriosis?


Potential New Target to Treat Endometriosis?

Scientists found that special cells called myeloid-derived suppressor cells could be playing a role in the development of endometriosis.

Key Points

Highlights:

Special cells called myeloid-derived suppressor cells (MDSC) could be playing a role in the development of endometriosis.

Importance:

These cells could be targeted to find a potential new treatment for endometriosis. 

Key results:

  • The number of MDSCs is significantly higher in the blood of patients with endometriosis as well as in the abdominal cavity of mouse models of endometriosis.
  • Most of the MDSCs found in the abdominal cavity of mice with endometriosis are granulocytic and express CXCR-2, ROS, and arginase. They also suppress T-cell proliferation.
  • The inactivation of MDSCs with antibodies dramatically suppresses the development of endometrial lesions.
  • In mice deficient in CXCR-2, MDSC induction, endometrial lesions, and angiogenesis are significantly decreased.
  • Adoptive transfer of MDSCs into CXCR2-2 deficient mice restores endometriotic growth and angiogenesis.

Limitations of the study:

These are early experiments performed in mice and the results may not necessarily be valid in humans. 

Lay Summary

Special cells called myeloid-derived suppressor cells (MDSC) could be playing a role in the development of endometriosis, suggests a study published in the European Journal of Immunology

These cells could, therefore, be targeted by novel therapeutic agents to treat endometriosis. 

MDSCs are a group of cells that originate from bone marrow stem cells. (Stem cells are unspecialized cells that can differentiate and give rise to any cell type in the body). MDSCs are cells that are still immature and that have the ability to suppress immune responses. They can also promote the formation of new blood vessels from existing ones. 

Researchers found that the number of MDSCs was significantly higher in the blood of patients with endometriosis. This led them to hypothesize that they could be playing a role in the development of this disease and that targeting them could constitute a potential therapeutic approach.

The researchers also found that MDCSs were increased in the abdominal cavity of mice in which they induced endometriosis, allowing them to conduct a series of experiments to test their hypotheses. 

First, they further characterized these cells. They found that most of them were granulocytic. (MDSCs are divided into two groups: granulocytic and monocytic depending on the proteins that are found on their surface). 

One of these proteins was CXCR-2, a receptor protein to which cell signaling molecules CXCL1, 2, and 5 bind to. These molecules were produced by endometrial lesions and “pulled” the MDSCs to the site of the lesion.

When the researchers inactivated MDSCs by using antibodies against them, they found that this dramatically suppressed the development of endometrial lesions in the mice.

They obtained similar results with mice that were genetically modified to ensure they could not produce CXCR-2. These animals showed significantly decreased MDSC induction, endometrial lesions, and angiogenesis, or new blood vessel formation, a biological event that is important in the development of endometriosis.

When they transferred MDSCs to the site of the lesion in the mice that could not produce CXCR-2, the researchers found that this restored the growth of the endometrial legions and blood vessel formation.

“Together, this study demonstrates that MDSCs play a role in the pathogenesis of endometriosis (…) thereby providing a potential target for endometriosis treatment” the researchers concluded.


Research Source: https://www.ncbi.nlm.nih.gov/pubmed/29460338


Myeloid-derived suppressor cells Angiogenesis Mouse model

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