“We already knew that fats in our blood, such as triglycerides and cholesterol, can influence the behavior of immune cells,” says professor of Biomedical Data Sciences Bas Heijmans. “We are now showing that these fats dampen the activity of genes that play a key role in allergies.” As a result, allergic reactions occur less quickly.
The researchers first mapped out which genes are active in immune cells in more than 3,200 people. “This turned out to be more than 17,000,” says Koen Dekkers, first author of the study. “We then investigated step by step which genes fats in the blood have an effect on, which led us to a group of genes that trigger allergic reactions.” Using an advanced analysis method in which the researchers combined blood levels of fats, gene activity and known genetic differences between people, they were able to demonstrate that this relationship is indeed causal.
An allergic reaction is characterized by an exaggerated response of your immune system to a harmless substance, such as pollen that leads to hay fever. The researchers found that fats mainly affect genes that are active in basophils. These are immune cells that, among other things, produce histamine and are crucial in triggering an allergic reaction.
More fat in our diet?
Triglycerides in particular have an effect on these basophils, the researchers discovered. The triglyceride level in the blood is partly determined by our DNA, but mainly by diet. “And that is of course very interesting,” says Heijmans. “This could mean that patients with severe allergic reactions might benefit from supplementing with extra triglycerides, or more precisely, the fatty acids that make up triglycerides.” But we are not there yet, emphasizes Heijmans. “First it must be tested whether and, if so, which fatty acids actually have these beneficial effects. Is it mainly the healthy, unsaturated fatty acids? That would be good news. Or the unhealthy, saturated fatty acids?” It is also not yet clear how fats change the behavior of immune cells in this direction.
Unexpected turn: from cardiovascular disease to allergy
Allergies were not exactly the area of expertise of Heijmans and Dekkers. “We therefore totally did not expect that this study would point us in that direction,” says Dekkers. Their arrows were aimed at cardiovascular diseases, in collaboration with Professor of Cardiology Wouter Jukema. “These diseases are driven by the interaction between fats and the immune system,” says Heijmans. “We expected to discover how fats influence genes involved in cardiovascular disease. But the effect on allergic reactions was even stronger.” So their research took an unexpected turn, but that doesn’t diminish their enthusiasm. Heijmans: “Such a surprising discovery is the icing on the cake for a scientist.”
Are allergies now becoming a new focus area in their research? Dekkers, who now works at Uppsala University in Sweden, does not rule it out for the longer term: “I certainly see further research in it, and I may just pick it up again later.” Heijmans: “Wouter Jukema and I are still interested in the effect of fats on immune cells, but are now focusing again on their role in cardiovascular disease.”
This research is a result of the national atherosclerosis consortium Genius, funded by the Heart Foundation and the Dutch CardioVascular Alliance. The research data used in this study have been brought together thanks to a collaboration between the VU University and the university medical centers of Rotterdam, Groningen, Maastricht, Utrecht and Leiden within BBMRI-NL.