Overlooked Immune Cells Trigger Preterm Labor
Tuesday, May 28, 2019
New IRP research has shed light on the role of certain immune cells in preterm labor, the leading cause of infant death globally. The study also provides evidence for a therapeutic approach to reduce the number of babies born too early.
Any baby born less than 37 weeks after conception is considered premature, but not all premature births have the same root cause. In a new study, IRP researchers have detailed how a particular component of the immune system can trigger premature labor, which could help doctors prevent more preterm births.1
Preterm labor is the leading cause of infant death worldwide. Premature babies are at greater risk for a wide array of health problems, including developmental delays, learning disabilities, and issues with vision, hearing, and breathing. The United States has a particularly high rate of preterm births among first-world countries, with roughly one in ten infants born too early.
In many cases, premature labor is caused by an inflammatory response that occurs when the body’s immune system reacts to a threat. That threat might be an infection that activates a part of the immune system called the ‘innate’ immune system, in which case doctors prescribe antibiotics. However, when researchers from the NIH’s Perinatology Research Branch (PRB) examined placentas from women who had gone into early labor, they found large numbers of immune cells called T cells2, which trigger a distinct inflammatory response through a separate branch of the immune system called the ‘adaptive’ immune system.
“Most of the research has focused on investigating how the innate immune system can be somehow blocked so that preterm birth is stopped,” explains PRB principal investigator and Wayne State University School of Medicine Associate Professor Nardhy Gomez-Lopez, Ph.D., the new study’s senior author. “The fact that there are T cells in the placenta and nobody had studied them before intrigued me. I thought that if the T cells were there, they must be there for a reason.”
The first part of her new study confirmed the PRB’s prior findings by looking for T cells in the layer of tissue that lines the uterus, called the decidua. Compared to tissue samples from women with normal pregnancies, decidua tissue from women who had experienced preterm labor contained many more effector T cells, the type of T cell that induces inflammation during an immune response. Those cells were also more active in tissue from the latter group of women, as shown by higher levels of certain damaging compounds the cells produce.
Next, the researchers examined three different rodent models of preterm labor: one that used a bacterial molecule to trigger a labor-inducing inflammatory response by the animals’ innate immune systems; one that caused preterm labor by spurring T cells to induce inflammation; and a third model that prompted premature labor through a mechanism that did not involve inflammation.
Premature labor induced by activating T cells caused several effects that were not seen when premature labor was prompted by triggering the innate immune system. For example, in the former model but not the latter, the researchers found activated T cells in the animals’ decidua, along with immune molecules called macrophages that were in a more inflammation-inducing state than in the other two models. Immune cells called neutrophils, however, were absent when inflammation and preterm labor were caused by activating T cells rather than stimulating the innate immune system.
“Some people might say by activating the T cells we’re causing the same sort of inflammation that occurs when an infection induces preterm birth,” Dr. Gomez-Lopez says. “What we showed is that activating the T cells causes inflammation in a similar way to an infection, but it also causes specific, unique responses. In other words, not all types of inflammation – and not all preterm labor and births – are the same.”
Finally, the research team gave the hormone progesterone to pregnant mice after inducing preterm labor by activating their T cells. Progesterone is used to halt premature labor in women with an uncommon condition called a ‘short cervix,’ and it similarly prevented premature labor in those mice by tamping down inflammation. This suggests that progesterone might help prevent premature labor in more women than was previously thought.
“Now we can take a strategy that is used for this small subset of patients with a short cervix and we can apply it to this other subset of women who have inflammation caused by T cells,” Dr. Gomez-Lopez says. “If we can expand that strategy, we can help more women.”
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References: Effector and Activated T Cells Induce Preterm Labor and Birth That Is Prevented by Treatment with Progesterone. Arenas-Hernandez M, Romero R, Xu Y, Panaitescu B, Garcia-Flores V, Miller D, Ahn H, Done B, Hassan SS, Hsu CD, Tarca AL, Sanchez-Torres C, Gomez-Lopez N. J Immunol. 2019; 202(9):2585-2608. doi: https://doi.org/10.4049/jimmunol.1801350.
 The frequency, clinical significance, and pathological features of chronic chorioamnionitis: a lesion associated with spontaneous preterm birth. Kim CJ, Romero R, Kusanovic JP, Yoo W, Dong Z, Topping V, Gotsch F, Yoon BH, Chi JG, Kim JS. Mod Pathol. 2010 Mar 26;23(7):1000-11. doi: 10.1038/modpathol.2010.73.