The immune system may need “continuing education” to protect the pregnancy

Researchers at UC San Francisco study how the immune system may play a role in miscarriage, affecting about a quarter of pregnancies.

Working on mice, researchers have discovered that a newly discovered subset of cells immune system it can prevent the mother’s immune system from attacking the placenta and fetus. If research is confirmed in other animal studies and cells play a similar role in humans, they could point the way to new therapies for pregnancies threatened by immune tolerance defects.

The researchers showed that pregnant mice that did not have this subset of cells, known as extraterrestrial cells that express air, were twice as likely to have miscarriages and, in many of these pregnancies, fetal growth. it was severely restricted.

“When she’s pregnant, the immune system sees the placenta for the first time in decades, not since the mother produced a placenta when she herself was a fetus,” said Eva Gillis-Buck, MD, a resident of UCSF surgery and first author of the work a Scientific immunology.

“Our research suggests that this subset of immune cells is carrying out a kind ofsecondary education‘- Sometimes many years after the best known population of educating cells has carried out the Primary Education in the thymus: teaches T cells not to attack the fetus, placenta and other tissues involved pregnancy. “

It is necessary to educate the immune system not to attack the tissues and organs themselves to prevent autoimmune diseases. But pregnancy presents a unique challenge, as the fetus expresses proteins found in the placenta and proteins whose genetics are different from the mother.

“It was a conceptual leap to link Air-expressing cells, which are critical to preventing autoimmune diseases, with pregnancy,” said Tippi Mackenzie, MD, professor of surgery and co-director of the Center for Maternal Fetal Precision Medicine. of the UCSF. author of the work. “This work hints at a mechanism for the known association between autoimmune diseases and pregnancy complications.”

Like the best-known thymus educator cells, the rare subset — originally discovered by James Gardner, MD, Ph.D., assistant professor of surgery, UCSF Diabetes Center researcher, and lead author of the study — known to its ability to express a unique protein called Autoimmune Regulator, or Air. Air has been extensively studied in the thymus, where it helps to define the curriculum of this “institute” for the immune system.

But the cells that express Air, which are being studied, reside outside the thymus in the lymph nodes and the spleen, so they are called extrathymic cells that express Air, or eTAC. Their role in the immune system is not entirely known, although UCSF scientists suspect they provide a mechanism for “continuing education.”

The discovery of pregnancy is the first evidence that eTACs play a role in maintaining normal immune tolerance. In the thymus, cells that express Air begin to interact with other immune cells very early in life to teach them what not to attack. The thymus begins to shrink and has almost disappeared in adulthood, at which time most immune cells have been educated.

But as the thymus shrinks, the eTAC population in the lymph nodes and spleen expands. The study suggests that a healthy pregnancy may depend on having these cells around you.

Clear the normal role of this peripheral population that expresses Air cells, the researchers used genetically modified mice from the Gardner lab to selectively remove eTACs during pregnancy.

“Understanding how the immune system is normally educated to distinguish‘ I ’from‘ not me ’is a very fundamental issue in biology,” Gardner said. “Once we know the basic wiring of this self-education system, we hope to do all sorts of powerful things, like modify the curriculum to improve pregnancy outcomes, prevent autoimmunity, or promote tolerance to transplanted organs.”