Targeting immune receptors to deplete myeloid-biased hematopoietic stem cells and rejuvenate the immune system

Stanford scientists have discovered that certain immune receptors become more active in hematopoietic stem cells with age. This change leads to increased production of myeloid cells in the bone marrow. By interfering with this process, researchers reduced the number of myeloid cells in the blood of older mice during an inflammatory response. This approach could potentially be used to treat autoimmune diseases and blood cancers like myeloid leukemia.

Hematopoietic stem cells (HSCs) in the bone marrow comprise two primary subsets: one that facilitates balanced production of myeloid and lymphoid cells, and another that exhibits a bias towards myeloid lineage production. The aging process is associated with a transition towards predominantly myeloid-biased HSCs, which leads to a cascade of physiological changes. These alterations include impaired T and B cell responses to novel pathogens, elevated chronic inflammation, increased incidence of hematopoietic disorders, and heightened cancer susceptibility due to compromised adaptive immune responses. This age-related HSC shift increases disease vulnerability in older populations. Targeting this hematopoietic imbalance could potentially enhance immune function and reduce disease susceptibility in the elderly.

When HSCs lacking the relevant immune receptors are transplanted into young mice, they produce significantly fewer myeloid cells compared to HSCs expressing these receptors. This holds for both mouse and human HSCs. Notably, inhibiting this immune signaling pathway reduces myeloid bias in aged mice and decreases the proportion of myeloid cells in the blood during an immune response. These findings suggest that selectively depleting myeloid-biased HSCs by modulating this immune axis could potentially treat autoimmune diseases and myeloid leukemias, as well as rejuvenate the aging immune system in humans.

Stage of Development:
Preclinical - in vivo data