PD‐1‐Enhanced Treg Cell Senescence in Advanced Maternal Age

Abstract Senescence occurs earlier in the immune system than in solid organs as age increases. Regulatory T (Treg) cells are among the first cells to exhibit signs of aging. However, whether advanced‐age pregnancy involves Treg cell aging remains unclear. This study demonstrated that the aging of women is accompanied by aging Treg cells and that PD‐1 regulates Treg cell aging. The transfer of young Treg cells can improve the pregnancy outcomes of reproductive‐aged mice by reducing the level of IFN‐γ, a proinflammatory cytokine secreted by Treg cells in aged mice. Transferring α‐PD‐1 mAb‐treated aged Treg cells increases the level of IL‐10, an anti‐inflammatory cytokine secreted by Treg cells in reproductive‐aged mice. Collectively, these findings suggest a potential therapeutic strategy for preventing adverse pregnancy outcomes in older women.