How your life story leaves epigenetic fingerprints on your immune cells

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

The COVID-19 pandemic gave us tremendous perspective on how wildly symptoms and outcomes can vary between patients experiencing the same infection. How can two people infected by the same pathogen have such different responses? It largely comes down to variability in genetics (the genes you inherit) and life experience (your environmental, infection, and vaccination history).

These two influences are imprinted on our cells through small molecular alterations called epigenetic changes, which shape cell identity and function by controlling whether genes are turned "on" or "off."

Researchers are debuting a new epigenetic catalog that reveals the distinct effects of genetic inheritance and life experience on various types of immune cells. The new cell type-specific database, published in Nature Genetics, helps explain individual differences in immune responses and may serve as the foundation for more effective and personalized therapeutics.

This work shows that infections and environmental exposures leave lasting epigenetic fingerprints that influence how immune cells behave. By resolving these effects cell by cell, we can begin to connect genetic and epigenetic risk factors to the specific immune cells where disease actually begins.

All the cells in your body share the same DNA sequence. And yet, there are many specialized cell types that look and act entirely differently. This diversity is due, in part, to a collection of small molecular tags called epigenetic markers, which decorate the DNA and signal which genes should be turned on or off in each cell. The many epigenetic changes in each cell collectively make up that cell's epigenome.

Unlike the base genetic code, the epigenome is far more flexible—some epigenetic differences are strongly influenced by inherited genetic variation, while others are acquired experientially across a lifetime. Immune cells are no exception to these forces, but it was unclear whether these two types of epigenetic changes—inherited versus experiential—affected immune cells in the same way.

Ultimately, both genetic inheritance and environmental factors impact us.

By collecting and analyzing blood samples from 110 individuals, the researchers were able to observe the effects of a variety of genetic profiles and life experiences, including flu; HIV-1, MRSA, MSSA, and SARS-CoV-2 infections; anthrax vaccination; and exposure to organophosphate pesticides.

The researchers then compared the epigenetic profiles of four major immune cell types: T and B cells, known for their long-term memory of past infections, and monocytes and natural killer cells, which respond more broadly and rapidly. From these many samples and cells, the team built a catalog of all the epigenetic markers, or differentially methylated regions (DMRs), in each cell type.

They found that disease-associated genetic variants often work by altering DNA methylation in specific immune cell types.

By mapping these connections, we can begin to pinpoint which cells and molecular pathways may be affected by disease risk genes, potentially opening new avenues for more targeted therapies.

The findings demonstrate the unique and substantial influence of both nature and nurture on immune cell identity and immune system performance. Furthermore, the catalog offers an exciting jumping-off point for creating new personalized treatment plans.

Wenliang Wang et al, Genetics and environment distinctively shape the human immune cell epigenome, Nature Genetics (2026). DOI: 10.1038/s41588-025-02479-6