In battle to shape immunity, environment often beats genes
Twin study shows microbes and other factors lead the immune system to adapt
GETTING A REACTION The immune system’s reaction to flu shots and infections is mostly determined by environmental, not genetic, factors.
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Environmental factors shape the immune system’s reactions more than genes do, a study of twins suggests. As people age, the effect of the environment on their immune systems grows even stronger, researchers report January 15 in Cell.
In the study, 58 percent of the variation measured in immune system responses was almost completely determined by nonheritable factors, such as exposure to microbes such as cytomegalovirus, a mostly benign virus that lives in 50 to 80 percent of adults.
The findings reinforce evidence that microbes have a powerful influence on the development of the human immune system. The lessons learned from this study also may lead to a better understanding of how genes and the environment interact, helping researchers figure out why some people get asthma, allergies or other autoimmune diseases, while others develop healthy immune reactions.
“It’s not negating that genetics can play a big role,” says immunologist Mark Davis of Stanford University. “We’re saying that inherited influences, genes, are not the whole story.”
WHAT WINS Environment more strongly determines numbers of immune cells in people’s blood than genes do. Researchers counted immune cells (each line is a different type of cell) in a large group of twins and calculated heritability, the amount variation of a trait that is due to genes. A heritability score of 0.00 indicates the variability is almost entirely due to environment, while a score of 1.00 indicates that the variability is determined by genetics. Many traits fall in between, with both genes and environment playing a role.
Source: P. Brodin et al/Cell 2015
Genes can predispose people to develop immune disorders, including asthma, type 1 diabetes, rheumatoid arthritis, psoriasis and many others. But not everyone who inherits a genetic susceptibility will actually develop the disorders. This study and others suggest that it also takes an environmental trigger, such as an infection, to set off the disease, says Janko Nikolich-Zugich, an immunologist at the University of Arizona in Tucson who studies aging and the immune system but was not involved in the new work. On the flip side, recent work has also demonstrated that microbes are essential to building a healthy immune system and may help prevent inflammatory bowel disease (SN: 8/10/13, p.14).
Davis and colleagues studied 210 healthy twins whose ages ranged from 8 to 82. Twins are often used to determine how much influence genes have on traits. Identical twins have nearly identical genetic makeup, while fraternal twins, like nontwin siblings, share about 50 percent of their genes. When a characteristic is more similar in identical twins than in fraternal twins, it indicates genetics is playing a bigger role than environment in shaping that trait. But if identical twins are no more similar than fraternal twins, environment and experience may be more important. Of the pairs studied, 78 were identical while 27 were fraternal.
The researchers measured 204 immune system characteristics, including numbers of various types of immune cells, levels of immune chemicals and proteins in the blood, and reactions to flu vaccines. Environment played the strongest role in 77 percent of the traits measured and is probably the sole determinant for 58 percent of them, the team found. For instance, genes played no detectable role in controlling how many antibodies people made against flu vaccines.
The study also showed that cytomegalovirus altered 119 of the 204 immune system reactions measured. “That virus single-handedly changes your immune parameters,” says Nikolich-Zugich.
Genes played a bigger role in the immune reactions of younger twins, the researchers found. But environmental factors gradually swamped that influence as the twins aged and lived apart, probably encountering different microbes. For instance, in identical twins younger than 20, blood levels of one type of immune cell, regulatory T cells, were 78 percent similar. But in twins 60 and older, the similarity had dropped to 24 percent.
“The scale [of the study] is absolutely stupendous,” says Stephen Kingsmore, who directs the Center for Pediatric Genomic Medicine at Children’s Mercy Hospital-Kansas City in Missouri. But there are some caveats that may weaken the conclusions, he says. The researchers studied only healthy people with no immune problems. Many previous studies have shown that autoimmune disorders are highly heritable. “You can study a billion molecules” and still not negate the fact that these disorders run in families, he says.
Even so, this study shows that microbes are the most powerful sculptors of the immune system, Nikolich-Zugich says, and that may be good news. Researchers studying human interactions with microbes may soon develop bacteria that can be used as therapies for a wide variety of ills, including immune disorders, he says. “You can blame your genes, but you might be able to modulate them with microbes.”
