Social adversity has profound biological effects in the individuals who experience it. Risk of physical injuries and food scarcity aside, it turns out that experiencing adversity changes how effectively immune cells combat infection. But this effect is reversible, a new study shows. The findings, published in the November 25 issue of Science, add to our understanding of how social status may influence health and survival, the researchers say.
The association between social adversity and poor health is not new, but its causes remain incompletely understood. In humans, those causes are hard to pin down because it would be challenging—not to mention unethical—to experimentally manipulate social rank in human societies. To get around this problem, Duke University evolutionary anthropologists Jenny Tung and Noah Snyder-Mackler and colleagues decided to study this question in rhesus macaques. “They combine something that is of real importance in human populations with a very tractable model that they could manipulate so beautifully,” says Michael Kobor, an epigeneticist at University of British Columbia who was not involved in the study.
To directly test the effect of social rank on health, the researchers introduced captive macaques into social groups with macaques previously unknown to each other. In general, the earlier a monkey is introduced to a group, the higher its social rank. After establishing the groups, the researchers drew blood samples from the monkeys and measured gene expression in the immune cells using RNA sequencing. They discovered that more than 1600 genes in NK (natural killer) cells were affected by social status.
Next, the researchers isolated immune cells from the monkeys and looked at the cells’ response to infection in vitro. They found that the immune cells from lower-ranking monkeys were less effective at combating the infection; these cells activated pro-inflammatory genes, whereas the cells from high-ranking monkeys activated the more effective anti-viral genes. “The body seems to respond to adversity with a fairly stereotyped reaction—at least at the genomic level—which generally involves increasing the expression of genes involved in inflammation and decreasing the expression of genes involves in protecting us against viral infection,” explains Steve Cole, UCLA neuro-immunologist who was not involved in the study.
But were those immune cells stuck in pro-inflammatory or anti-viral modes? When the researchers scrambled the macaques’ rank by creating new groups, they found that the gene expression levels in immune cells quickly changed in response to the monkeys’ new social rank. “A change in social status is rapidly reflected in that individual’s gene expression profile,” explains Snyder-Mackler.
Previous studies in humans have shown that early life adversity can have lasting effects on health. Some of these effects are mediated by the same genetic pathways that were identified in this study. Kobor’s team has found, for example, that pro-inflammatory transcription factors continue to be upregulated in people who grew up in low socio-economic status conditions—irrespective of their current socio-economic status. “So that suggests that early-life socio-economic status can ‘get under the skin’ to affect health, behavior, and immune function throughout life,” says Kobor. The current findings pose an interesting question about whether some of the detrimental effects of early life poverty could possibly be reversed, he says.