An important risk factor for asthma is that your own mother also has asthma. However, the underlying mechanisms were unclear. A new study now shows that adult asthmatics whose mothers also had asthma have specific epigenetic patterns on their DNA that are not found in asthmatics with healthy mothers. The changes particularly affect certain immune signaling pathways. The researchers assume that certain epigenetic patterns that can later lead to asthma are probably formed during pregnancy.
The foundations of our looks, our abilities, and our character are encoded in our genes. However, which genes are transcribed and to what extent is regulated by so-called epigenetic modifications. Influenced by environmental factors, certain molecules are attached to the DNA, causing some genes to be read more while others are silenced. One of the most important epigenetic modifications is the so-called methylation. Methyl groups consisting of one carbon atom and three hydrogen atoms bind to certain parts of the DNA and prevent the subsequent gene from being read.
epigenetic differences
A team led by Kevin Magnaye from the University of Chicago has now examined the methylation pattern in the DNA of asthma patients in order to find out what role epigenetic changes play in the development of this widespread respiratory disease. Since it was already known that maternal asthma is an important risk factor, the researchers compared asthma patients whose mother had asthma with asthma patients whose mother did not have asthma, and with healthy subjects. Epithelial cells from the test subjects’ lower respiratory tract served as test material.
In fact, the researchers found clear differences between the groups of subjects: “The methylation patterns in those with asthmatic mothers were associated with reduced expression of genes belonging to signaling pathways in the immune system,” reports Magnaye. The signaling pathways that have been suppressed in the asthmatic patients with asthmatic mothers are associated with impaired T cell signaling. T cells are part of the adaptive immune system and are involved in the immune response to viruses and bacteria, among other things. This suggests that the genetic changes have something to do with asthma, which is characterized by deregulation of the immune system.
Changes already in the womb?
The results on the methylation patterns were confirmed in another study in which epithelial cells from the airways of children with asthma were examined. The researchers therefore suspect that the corresponding epigenetic changes do not only occur over the course of life, but are already determined during pregnancy by the environment of the fetus in the uterus of an asthmatic patient. “The fact that the results were repeated in a separate children’s cohort supports the notion that these changes are present long before adulthood,” says Magnaye’s colleague Carole Ober.
In order to substantiate this hypothesis, the researchers want to accompany children of asthmatic mothers from infancy in future studies and track how the corresponding epigenetic changes affect them over the course of their lives. In addition, the team is currently working on decoding possible interactions between the microbiome, epigenetics and the development of asthma.
Opportunity for more effective therapies
The epigenetic changes were associated with so-called type 2 asthma, a severe form of asthma that does not respond to standard treatment with corticosteroids. “This subtype of asthma is particularly difficult to treat,” Ober explains. “Our results suggest that the underlying cause is an impaired immune response, which may explain the lack of therapeutic response to corticosteroids.” From Ober’s point of view, this could open up new avenues for possible therapies. The standard therapy aims to suppress excessive immune reactions and thus have an anti-inflammatory effect. “However, in certain patients, immune-enhancing therapies may be more effective than immunosuppressive therapies,” the researchers said.
Source: Kevin Magnaye (University of Chicago, USA) et al., Proceedings of the National Academy of Sciences, doi: 10.1073/pnas.2116467119