A recent study published in Nature Genetics has mapped how both inherited DNA and environmental exposures shape the human immune system through distinct epigenetic changes. Researchers created a detailed atlas by analyzing blood samples from 110 donors who had been exposed to pathogens like HIV and COVID-19 or chemicals such as pesticides.
The study found that genetic factors primarily affect gene bodies in memory immune cells, while environmental influences tend to modify regulatory regions—enhancers and promoters—in naive immune cells. These differences suggest that genetics and environment impact different parts of the genome, each contributing uniquely to immune function and disease risk.
"For HIV-1 and IAV, we have internal control samples that are from the same set of donors before infection and collected samples from them after exposure. We also collected PBMC from 12 healthy donors as external controls. For exposures without internal controls (COVID, anthrax vaccine, MRSA/MSSA and OP), all healthy samples were used as controls. We performed snATAC–seq and snmC-seq2 on the PBMCs and identified the eDMRs associated with exposures and genotypes. We also identified the gDMRs using this dataset. BA, B. anthracis. The figure is created with BioRender.com."
Using single-cell sequencing techniques, scientists sorted participants’ blood into seven major immune cell types—including T cells, B cells, natural killer (NK) cells, and monocytes—and further divided these into naive or memory states along with other subtypes.
Analysis revealed over 756,000 environmental methylation markers (eDMRs) mostly located in regulatory regions of DNA that control gene activity, while more than 275,000 genetic markers (gDMRs) were found mainly within gene bodies responsible for coding proteins.
The research highlighted several findings: Environmental effects were stronger in naive lymphocytes; genetic factors had more influence on memory lymphocytes; prior HIV-1 infection led to significant changes in NK cells and memory T cells; severe COVID-19 was linked to a specific monocyte cluster strongly associated with inflammation; individuals of African ancestry showed greater methylation changes following certain infections compared to those of European ancestry; finally, some genotype-related methylation sites overlapped with known disease-risk loci for conditions like eczema and gallstone disease.
According to the authors, "The present study provides evidence that nature and nurture are distinct architects of immune cell biology. Although their effects converge on immune function, genetic variation and environmental exposures appear to operate through mechanistically and genomically separate pathways."
Researchers note that while this atlas may advance personalized medicine by linking epigenetic patterns to health outcomes, further studies are needed to confirm these findings due to limitations such as incomplete exposure histories or smaller sample sizes in some groups.
