By studying a population of twins, scientists based at King’s College London have revealed surprising and even paradoxical findings about our immune system. The part of our immune system that learns to respond to specific pathogens—the adaptive immune system—is mainly shaped by genetic factors. And the part of our immune system that stages more generic responses to external threats—the innate immune system—is mainly shaped by environmental factors.

At first glance, it may seem odd that our adaptive immunity, our most complex and discriminating means of responding to environmental threats, should rely so much on in-born attributes, whereas our innate immunity, which is, well, “innate,” should be more sensitive to environmental differences than genetic variations. But these findings are what emerged from an expansive study that analyzed 23,394 immune traits in 497 adult twins.

Details of the study appeared January 5 in the journal Nature Communications, in an article entitled, “Innate and Adaptive Immune Traits Are Differentially Affected by Genetic and Environmental Factors.” The study covers the representation and phenotype of all major lymphocyte and myeloid subsets in the peripheral blood. It also provides insight into the homeostatic mechanisms governing the balance of immune cells. Finally, it has implications for research into personalized therapies, as well as the development of treatments for autoimmune diseases such as rheumatoid arthritis and psoriasis.

Of the traits considered in the study, “76% … show a predominantly heritable influence, whereas 24% are mostly influenced by environment,” wrote the study’s authors. “These data highlight the importance of shared childhood environmental influences such as diet, infections, or microbes in shaping immune homeostasis for monocytes, B1 cells, γδ T cells, and NKT cells, whereas dendritic cells, B2 cells, CD4+ T and CD8+ T cells are more influenced by genetics.”

“Although leukocyte subsets are influenced by genetics and environment,” the authors added, “adaptive immune traits are more affected by genetics, whereas innate immune traits are more affected by environment.”

The King’s scientists noted that they took advantage of the twin structure of their cohort, the TwinsUK cohort, to model the common environmental influence on the same traits. The scientists asserted that their analysis allowed then to ascribe the proportion of the variation of any given trait that is explained by heritable or genetic influences, shared common environmental influences, or by unshared environmental influences or simply stochastic in nature.

“Our genetic analysis resulted in some unusual findings, where adaptive immune responses, which are far more complex in nature, appear to be more influenced by variations in the genome than we had previously thought,” said Massimo Mangino, a King's researcher and the article’s lead author. “In contrast, variation in innate responses (the simple nonspecific immune response) more often arose from environmental differences. This discovery could have a significant impact in treating a number of autoimmune diseases.”

“Our results surprisingly showed how most immune responses are genetic, very personalized, and finely tuned,” added Tim Spector, director of the TwinsUK Registry at King's, and the article’s senior author. “What this means is that we are likely to respond in a very individualized way to an infection such as a virus—or an allergen such as a house dust mite causing asthma. This may have big implications for future personalized therapy.”

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