Abstract
Abstract Aging is the single most important prognostic factor for the development of many cancers. While mutational accumulation may increase the risk of cancer in aged individuals, declining immunity due to chronic inflammation is also a likely contributing factor. We have demonstrated that reducing aging-associated chronic inflammation abrogates fitness declines in B-progenitor cells, and significantly reduces leukemogenesis in aged mice (Henry et al., JCI, 2015). In addition to preserving the function of B-progenitor cells, subsequent studies have revealed that reducing chronic inflammation in aged mice augments immune responses. Specifically, reducing inflammation in aged mice (≥22 months) results in a two-fold reduction in the number of splenic M2 macrophage and T-regulatory cell populations, as well as, a three-fold reduction in the surface expression of the inhibitory protein PD-L1 on innate immune cells. Reducing chronic inflammation in aged mice also results in a three-fold increase in the percentage of interferon-gamma producing CD4+ and CD8+ T-cell lymphocytes when stimulated. These phenotypes were observed in aged, anti-inflammatory transgenic mice (alpha-1-anti-trypsin and interleukin-37) and in geriatric mice (≥27 months) treated with recombinant interleukin-37. Overall, these findings suggest that reducing chronic inflammation in aged populations can rejuvenate hematopoiesis and immunity, while also creating a less permissive environment for leukemogenesis.
Published Version
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