Early age-related atrophy of cutaneous lymph nodes precipitates an early functional decline in skin immunity in mice with aging

Abstract

Significance: Older adults are more vulnerable to infection and less capable of vigorously responding to vaccination. The contribution of peripheral T cell maintenance defects to these processes is incompletely understood. Here, we provide evidence that lymph nodes (LNs), which are critical for naive T (TN) cell maintenance and initiation of new immune responses, age asynchronously. Skin-draining LNs undergo early (6 to 9 mo) and deeper LN and spleen late-life (18 mo) atrophy, characterized by reduced ability to maintain TN cells, structural and numerical loss of LN stromal cell microenvironments, and reduced immunity to cutaneous vaccination. These results highlight the critical role of age-related LN atrophy in functional immunity and immune homeostasis.