Inflammation may cause lasting epigenetic changes in blood stem cells

Blood stem cells can retain a long-term 'memory' of inflammatory events, which may help explain links between ageing, chronic disease and blood cancers.

The study, published in the journal Nature, identified a distinct subset of blood stem cells that undergo long-lasting epigenetic changes in response to inflammation. Rather than fully returning to their original state after inflammatory stress, some of these cells retain molecular signatures that reflect past exposure. Over time, these cells accumulate and may influence how the immune system functions later in life.

'This study gives us a new way to think about how the body's past experiences of inflammation may shape future health. Blood stem cells are long-lived, and our findings suggest they can carry a molecular record of inflammatory stress, one that may help explain why people of similar ages can have very different risks of age‑related disease' said Professor Philip Awadalla, co-director of the Translational Epidemiology Unit at Oxford Population Health, who was a senior author on the study.

Blood stem cells are responsible for producing all blood and immune cells, but how they respond to and recover from inflammatory stress was not well understood. In this study, researchers at the University of Oxford, working with collaborators based in Canada, Portugal and the USA, used a combination of mouse models carrying human blood stem cells and analyses of human bone marrow samples to track these responses over time.

They identified two main populations of blood stem cells with distinct genetic and epigenetic profiles following inflammatory exposure. One population returned to its baseline state once inflammation resolved, while a second population – described as an 'inflammatory memory' subset – retained stable epigenetic changes and continued expression of inflammation-related genes long after the initial trigger had passed.

Inflammatory memory blood stem cells were found more frequently in healthy adults over the age of 40. They were also associated with mutations known to increase the risk of leukaemia. These mutations appeared to keep the cells in a more active state and may promote their expansion under inflammatory conditions. In addition, they were linked to chronic inflammatory conditions, including severe COVID-19 and sickle cell disease, suggesting a broader role in disease susceptibility.

The researchers also observed similar genetic changes in immune cells derived from inflammatory memory stem cells, indicating that this inflammatory 'memory' can be passed on as stem cells differentiate into mature blood cells.

Further research is needed to fully understand how these inflammatory memory stem cells arise and how they contribute to disease. However, their identification provides a new framework for studying how inflammation, ageing and cancer risk may be connected at the level of the blood system.