New findings provide insight on long-standing pregnancy mystery
Researchers at NYU School of Medicine have made an important discovery that partially answers the long-standing question of why a mother's immune system does not reject a developing fetus as foreign tissue.
"Our manuscript addresses a fundamental question in the fields of transplantation immunology and reproductive biology, namely, how do the fetus and placenta, which express antigens that are disparate from the mother, avoid being rejected by the maternal immune system during pregnancy?" explained lead investigator 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 embryo 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 defense against transplanted foreign tissues and pathogens is the production of chemokines as a result of the local inflammatory response. The chemokines recruit various kinds of immune cells, including activated 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 evoke the typical tissue rejection response seen with organ transplants.
Several years ago, Erlebacher and his research team found that T cells, poised 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 specialized structure that encases the fetus and placenta, and there, in a mouse model, they found new answers.
The research team has discovered that the onset of pregnancy causes the genes 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 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 nuclei of the developing decidua's stromal cells. The change in the DNA packaging permanently deactivates, or "silences," the chemokine genes. Consequently, the chemokines are not expressed and T cells are not recruited to the site of embryo implantation.
Also of note, the observed change in the DNA packaging was a so-called 'epigenetic' modification, meaning a modification that changes gene expression without the presence of a hereditable gene mutation.
"These findings give insight into mechanisms of fetal-maternal immune tolerance, as well as reveal the epigenetic modification of chemokine genes within tissue stromal cells as a modality for limiting the trafficking of activated T cells," Dr. Erlebacher said. "It turns out that the cells that typically secrete the chemoattractants to bring the T cells to sites of inflammation are inhibited from doing so in the context of the pregnant uterus. The decidua appears instead as a zone of relative immunological inactivity."
Inappropriate regulation of this process, Dr. Erlebacher explained, could cause inflammation and the accumulation of immune cells at the maternal-fetal interface, which could lead to complications of human pregnancy, including preterm labor, spontaneous abortion and preeclampsia.
Erlebacher and his team will next look to see if these epigenetic modifications are also present within the human decidua, and whether the failure to generate them appropriately is associated with complications of human pregnancy. He explained that the study's findings also raise the possibility that the same kind of mechanism could enhance a tumor's ability to survive inside its host. The findings could have implications for autoimmune diseases, organ transplantation and cancer, as well as pregnancy.
"This is a very exciting finding for us because it gives a satisfying explanation for why the fetus isn't rejected during pregnancy, which is a fundamental question for the medical community with clear implications for human pregnancy," Dr. Erlebacher said. "It also reveals a new modality for controlling T cell trafficking in peripheral tissues that could provide insight into a myriad of other conditions and diseases."
More information: "Chemokine Gene Silencing in Decidual Stromal Cells Limits T Cell Access to the Maternal-Fetal Interface," by P. Nancy et al., Science, 2012.
Journal reference: Science
Provided by New York University School of Medicine
- Three types of fetal cells can migrate into maternal organs during pregnancy Jun 06, 2012 | not rated yet | 0
- Researchers may have discovered key to help women fight infections during pregnancy Jul 21, 2011 | not rated yet | 0
- Researchers find new source of immune cells during pregnancy Dec 16, 2010 | not rated yet | 0
- Mother's stem cells likely key to treating genetic disease before birth Jan 18, 2011 | not rated yet | 0
- Researchers Show How Active Immune Tolerance Makes Pregnancy Possible Jul 01, 2010 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Pressure-volume curve: Elastic Recoil Pressure don't make sense
20 hours ago From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013 As an experiment, for the past few months I've been consuming at least one portion of Jell-O or unflavored Knox gelatin per day. I'm 64, in very...
Alcohol and acetaminophen
May 13, 2013 Edit: sorry for the typo in the title , can't edit I looked around on google quite a bit and it's very hard to find precise information on the...
Marie Curie's leukemia
May 13, 2013 Does anyone know what might be the cause of Marie Curie's cancer
- More from Physics Forums - Medical Sciences
More news stories
In 2008 researchers from the University of Southern Denmark showed that the drug thioridazine, which has previously been used to treat schizophrenia, is also a powerful weapon against antibiotic-resistant bacteria such as ...
Medical research May 17, 2013 | 3.7 / 5 (3) | 0 |
Scientists investigating the interaction of a group of proteins in the brain responsible for protecting nerve cells from damage have identified a new target that could increase cell survival.
Medical research May 17, 2013 | 5 / 5 (1) | 0
New findings by researchers carrying out experiments at the U.S. Department of Energy Office of Science's Advanced Photon Source (APS) help explain why some drugs that interact with two kinds of human serotonin ...
Medical research May 17, 2013 | not rated yet | 0 |
Peptide molecules derived from the body's natural immune system can help boost the body's defence against life-threatening blood poisoning, joint University research has uncovered.
Medical research May 17, 2013 | 4 / 5 (1) | 0 |
A new Montréal study conducted by Dr. May Faraj, associate research professor at the Université de Montréal and invited scientist at the IRCM, along with her research team and medical collaborators, shows ...
Medical research May 17, 2013 | not rated yet | 0 |
An increasing number of U.S. children are experiencing gastrointestinal issues that require interventions to resolve, according to research presented at Digestive Disease Week (DDW).
13 hours ago | not rated yet | 0 |
The latest makeover to a massive psychiatric tome honored by some, reviled by others and even called the "Bible" of mental disorders is being released Saturday with a host of new changes.
10 hours ago | not rated yet | 0
A new case of the deadly coronavirus has been detected in Saudi Arabia where 15 people have already died after contracting it, the health ministry announced on Saturday on its Internet website.
10 hours ago | not rated yet | 0
Big names in medicine are set to give an upbeat assessment of the war on AIDS on Tuesday, 30 years after French researchers identified the virus that causes the disease.
21 hours ago | 5 / 5 (1) | 0
For combat veterans suffering from post-traumatic stress disorder, 'fear circuitry' in the brain never rests
Chronic trauma can inflict lasting damage to brain regions associated with fear and anxiety. Previous imaging studies of people with post-traumatic stress disorder, or PTSD, have shown that these brain regions can over-or ...
22 hours ago | 5 / 5 (1) | 0 |
A ground-breaking advance in colonoscopy technology signals the future of colorectal care, according to research presented today at Digestive Disease Week(DDW). Additional research focuses on optimizing the minimal withdrawal ...
13 hours ago | 5 / 5 (2) | 0