Stem cells in the blood can retain a molecular 'memory' of inflammation that may increase the risk of age-related disease, according to a new study led by researchers at the University of Toronto and the University of Oxford. The study is published today in Nature.
The researchers found that some blood stem cells can hold a durable imprint of inflammatory stress long after the initial trigger has passed. This "inflammatory memory" may accumulate across a lifetime, contributing to differences in how people age, recover from severe infection, and develop blood-related conditions.
Blood stem cells sit at the top of the blood and immune system, producing the many cell types that the body needs throughout life including immune cells that respond to infection and injury. While inflammation is essential for fighting infection and repairing damage, repeated or severe inflammatory stress can also have lasting effects on health.
The study identifies a distinct type of blood stem cell, now termed HSC-iM (haematopoietic stem cell inflammatory memory), which showed lasting molecular changes following inflammatory challenge. The researchers drew on experimental models of inflammation and recovery, single-cell genomic technologies to identify stem cells carrying signals associated with inflammation, ageing, severe infection, sickle cell disease, and clonal haematopoiesis. Clonal haematopoeisis is an age-related condition in which some blood stem cell clones expand disproportionately, raising the risk of blood cancers and other chronic diseases.
Professor Philip Awadalla, Oxford Population Health, said:
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.’
Analyses of patient and population datasets were able to confirm that inflammatory memory was not confined to the stem cells themselves as some of the immune cells they produced also carried inflammatory signals. In population cohort-level analyses, inflammatory memory signatures in circulating blood cells were associated with a risk linked to all-cause mortality, suggesting these changes may have broader relevance for long-term health.
Professor Paresh Vyas, from the MRC Weatherall Institute of Molecular Medicine and Oxford Centre for Haematology, said:
Inflammation is part of normal immune defence, but our study shows that its effects on blood stem cells can persist. Understanding this memory may be important for explaining how chronic inflammatory conditions, severe infections, and age-related blood changes become linked over time.’
Ultimately, the findings offer a cellular framework for one of medicine's most persistent puzzles: why people of the same age can have such different health outcomes.