Attenuating age-related decline in dendritic cell migration improves vaccine efficacy via gut-immune crosstalk.

Aging impairs immune function and reduces vaccine efficacy, but whether dendritic cells (DCs), which play a central role in initiating immune responses via antigen presentation, contribute to this decline remains unclear. Through single-cell RNA sequencing analysis of lymph node changes upon vaccination in young versus aged mice, here we identify defects in DC migration during aging, alongside a dysfunction-associated gene signature in migratory DCs, and implicate these defects in the diminished vaccine response observed in aging. Furthermore, we demonstrate that oral delivery of yeast-derived nanoparticles elevates expression of the chemokine receptor CCR7 in gut dendritic cells, facilitates their trafficking to lymph nodes in response to chemotactic signals after immunization, and thus enhances vaccine-induced immunity in aged animals. These findings reveal a key mechanism of immune decline in aging and offer a noninvasive strategy to improve dendritic cell function and vaccine efficacy in aging.