Sing Sing Way, MD, PhD.

Sing Sing Way, MD, PhD

Preclinical research demonstrates that refocusing an expectant mother’s immune cells to prevent them from attacking the fetus may help prevent some premature births and stillbirths.

Findings were published March 9, 2015, in The Journal of Clinical Investigation. The study suggests that preventing pregnancy complications may be a delicate balancing act between sustaining the maternal-fetal immune system while reducing risk of causing harm to the fetus.

“Pregnant women are especially susceptible to infection, so it might seem counter-intuitive to prevent their immune cells from properly penetrating placental tissues,” says senior study author Sing Sing Way, MD, PhD, a researcher in the Division of Infectious Diseases at Cincinnati Children’s. “However, we found that pregnancy complications largely stem from harmful maternal immune cells that recognize and attack the placenta and other immunologically foreign tissues derived from the fetus. Restricting the access of harmful immune cells to developmentally delicate fetal tissue represents a highly innovative therapeutic strategy.”

A team led by Way and first author Vandana Chaturvedi, PhD, used mouse models to evaluate pregnancy outcomes after causing infections with Listeria monocytogenes. When infections began, researchers noted that early responding neutrophils and macrophages produced high levels of the CXCL9 protein, which in turn attracted harmful T cells that attacked the fetus. This finding is significant because placental cells are normally programmed not to express chemoattractant proteins like CXCL9.

The researchers found two ways to neutralize CXCL9 activity by blocking its receptor on T cells. Both methods prevented Listeria infections from causing stillbirths in treated mice. Importantly, the team found that neutralizing CXCL9 also helped prevent some pregnancy complications that were not caused by infections.

These findings indicate that preventing harmful immune cells from entering the placenta may have broad applications. As a next step, Way and colleagues plan to evaluate the pregnancy protecting ability of a class of small molecule inhibitors that already are being tested as treatments for human autoimmune and inflammatory disorders.