Researchers at the Salk Institute have developed a detailed epigenetic catalog of human immune cells, showing how genetics and life experiences influence immune responses differently. The study, published in Nature Genetics, analyzed samples from 110 diverse individuals to distinguish inherited from environmental epigenetic changes. This work could lead to personalized treatments for infectious diseases.
The COVID-19 pandemic highlighted stark differences in how people respond to the same virus, prompting scientists to investigate the roles of genetics and life experiences in immune function. A team led by Joseph Ecker, PhD, at the Salk Institute created an epigenetic map that reveals these factors shape immune cells through molecular modifications without changing DNA sequences.
The researchers examined blood samples from 110 people, reflecting varied genetic backgrounds and exposures such as flu, HIV-1, MRSA, MSSA, SARS-CoV-2 infections, anthrax vaccination, and organophosphate pesticides. They focused on four key immune cell types: T cells and B cells, which maintain long-term memory, and monocytes and natural killer cells, which react swiftly to threats.
By identifying differentially methylated regions (DMRs), the study separated genetically driven changes (gDMRs), often near stable gene regions in T and B cells, from experience-driven ones (eDMRs), concentrated in regulatory areas for rapid responses. "Our immune cells carry a molecular record of both our genes and our life experiences, and those two forces shape the immune system in very different ways," Ecker stated.
Co-first author Wubin Ding, PhD, noted, "We found that disease-associated genetic variants often work by altering DNA methylation in specific immune cell types." This catalog, published on January 27, 2026, in Nature Genetics, offers a resource for linking genetic risks to immune cells and could enable predictions of infection outcomes, such as for COVID-19, to inform tailored prevention strategies.
Wenliang Wang, PhD, another co-first author, emphasized the potential: "Our work lays the foundation for developing precision prevention strategies for infectious diseases." The findings underscore how epigenomes adapt over time, providing insights into personalized medicine without speculating on untested applications.
