新研究阐释长期存在的妊娠奥秘

Researchers at NYU School of Medicine have made an important discovery that partially¹ answers the long-standing question of why a mother's immune system does not reject a developing fetus² as foreign tissue. "Our manuscript（手写的） addresses a fundamental question in the fields of transplantation immunology and reproductive biology, namely, how do the fetus and placenta（胎盘） , which express antigens that are disparate from the mother, avoid being rejected by the maternal³ immune system during pregnancy⁴?" explained lead investigator⁵ Adrian Erlebacher, MD, PhD, associate professor of pathology and a member of the NYU Cancer Institute at NYU Langone Medical Center. "What we found was completely unexpected at every level."

The researchers discovered that embryo⁶ implantation sets off a process that ultimately turns off a key pathway required for the immune system to attack foreign bodies. As a result, immune cells are never recruited to the site of implantation and therefore cannot harm the developing fetus.

The study, funded by grants from the National Institutes of Health and the American Cancer Society, appears in the June 8 issue of Science.

A central feature of the body's natural immune defense⁷ against transplanted foreign tissues and pathogens is the production of chemokines（趋化因子） as a result of the local inflammatory（炎症的） response. The chemokines recruit various kinds of immune cells, including activated⁸ T cells, which accumulate and attack the tissue or pathogen. The chemokine-mediated recruitment of activated T cells to sites of inflammation is an integral part of the immune response.

During pregnancy however, the foreign antigens of the developing fetus and the placenta come into direct contact with cells of the maternal immune system, but fail to evoke⁹ the typical tissue rejection¹⁰ response seen with organ transplants.

Several years ago, Erlebacher and his research team found that T cells, poised¹¹ to attack the fetus as a foreign body, were somehow unable to perform their intended role. The finding prompted the researchers to wonder if perhaps there was some sort of barrier preventing the T cells from reaching the fetus. They turned their attention to studying the properties of the decidua, the specialized¹² structure that encases the fetus and placenta, and there, in a mouse model, they found new answers.

The research team has discovered that the onset¹³ of pregnancy causes the genes¹⁴ that are responsible for recruiting immune cells to sites of inflammation to be turned off within the decidua. As a result of these changes, T cells are not able to accumulate inside the decidua（蜕膜） and therefore do not attack the fetus and placenta.

Specifically, they revealed that the implantation of an embryo changes the packaging of certain chemokine genes in the nuclei¹⁵ of the developing decidua's stromal cells. The change in the DNA¹⁶ packaging permanently¹⁷ deactivates¹⁸, or "silences," the chemokine genes. Consequently, the chemokines are not expressed and T cells are not recruited to the site of embryo implantation.