In a new paper published in Cellular & Molecular Immunology, USC Stem Cell scientist Rong Lu and her collaborators have identified a small subset of blood stem cells that play a crucial role in maintaining the balance between innate and adaptive immune cells, which is essential for a youthful and effective immune system. The innate immune cells are the body’s first line of defense, while adaptive immune cells provide a specific and targeted response to pathogens based on past infections. A healthy balance between these two types of immune cells is crucial for longevity and disease prevention.
The study found that when a small subset of blood stem cells overproduces innate immune cells, it can lead to immune aging, disease, and a shortened lifespan. By tracking individual blood stem cells responsible for producing both types of immune cells, the researchers discovered that changes in the preferences of these cells as the mice aged played a significant role in the imbalance of the immune system. Specifically, thirty to forty percent of blood stem cells changed their preference for producing innate versus adaptive immune cells with age.
In delayed agers, the subset of blood stem cells reduced their production of innate immune cells, protecting against the effects of aging. This was associated with increased gene activity related to the regulation and response to external signals in these cells. In contrast, early agers showed a shift towards producing more innate immune cells, leading to an increased risk of age-related diseases. Using CRISPR technology, the researchers were able to edit out genes associated with early aging and promote the production of adaptive immune cells instead.
The findings of the study have important implications for the aging human population, where an overabundance of innate immune cells is often observed in elderly individuals. This imbalance can contribute to diseases such as myeloid leukemia and immune deficiencies. By promoting a more youthful immune system, it may be possible to combat these common diseases of aging. The study highlights the potential for targeting the subset of blood stem cells responsible for the imbalance in immune cell production as a strategy to delay immune aging and promote longevity.
The research was supported by federal funding from the National Institutes of Health and the National Cancer Institute, as well as grants from the California Institute for Regenerative Medicine and the Leukemia & Lymphoma Society. The study sheds light on the underlying mechanisms of immune aging and provides insights into potential interventions to promote a more youthful immune system and prevent age-related diseases. The identification of the subset of blood stem cells responsible for the imbalance in immune cell production offers new opportunities for targeted therapies to improve immune function and overall health in aging individuals.