Abstract
BackgroundAging is associated with a decline in lymphocyte function however, little is known about dendritic cell (DC) subsets and aging. Aging is also associated with increasing circulating lipid levels and intracellular lipid accumulation modulates DC function. Whether age-associated increases in lipid levels influence DC biology is unknown. Thus, the effects of aging on DC subsets were assessed in vivo using young adult and elderly C57BL/6 J mice.ResultsMajor age-related changes included increased CD11c+ DC numbers in lymph nodes, spleens and livers, but not lungs, and significantly increased proportions of plasmacytoid (pDC) and CD4-CD8α+ DCs in lymph nodes and livers. Other changes included altered pDC activation status (decreased CD40, increased MHC class-I and MHC class-II), increased lipid content in pDCs and CD4-CD8α+ DCs, and increased expression of key mediators of lipid uptake including lipoprotein lipase, scavenger receptors (CD36, CD68 and LRP-1) in most tissues.ConclusionsAging is associated with organ-specific numerical changes in DC subsets, and DC activation status, and increased lipid content in pDCs and CD4-CD8α+ DCs. Up-regulation of lipoprotein lipase and scavenger receptors by lipid-rich pDCs and CD4-CD8α+ DCs suggests these molecules contribute to DC lipid accumulation in the elderly. Lipid accumulation and modulated activation in pDCs and CD4-CD8α+ DCs may contribute to the declining responses to vaccination and infection with age.
Highlights
Aging is associated with a decline in lymphocyte function little is known about dendritic cell (DC) subsets and aging
CD11c+ DC proportions increase in elderly murine tissues Spleens, lymph nodes (LNs) from different sites, lungs and livers from young and elderly mice were disaggregated into single cell suspensions and stained for CD11c+ DCs (Figure 1A)
Studies on age-related changes to DC numbers and activation status are conflicting. This is true for human studies of circulating DC subsets; some have shown a significant decrease in circulating pDC numbers with no change in myeloid DC numbers [19,20,21,22], whilst others reported a decrease in myeloid DC populations with no change in pDC numbers [23]
Summary
Aging is associated with a decline in lymphocyte function little is known about dendritic cell (DC) subsets and aging. Aging is associated with increasing circulating lipid levels and intracellular lipid accumulation modulates DC function. Aging is associated with a decline in immune function, termed immunosenescence, which results in decreased vaccine efficacy and increased incidence of infection, cancer and autoimmunity [1,2,3,4]. This decrease in immune competence has been attributed to age-related changes to the numbers and function of T- and B-lymphocytes [2]. Tissue DCs in otherwise healthy elderly hosts might be exposed to elevated lipid levels leading to DC lipid accumulation. It is possible that lipidmediated DC dysfunction might contribute to the agerelated decline in immune function and that this might be an early event that precedes the development of agerelated pathologies
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