Aging is associated with altered dendritic cells subset distribution and impaired proinflammatory cytokine production

Abstract

Aging is characterized by the gradual decline in immune function. Dendritic cells (DC) are potent antigen-presenting cells that regulate the balance between immunity and tolerance. The reduction in immune responsiveness and increased susceptibility to infections observed in the aged population could be due to age-related defects in DC differentiation and function. In this study, we examined the effects of aging on DC subset frequency, antigen-presenting function, and activation using physiologically relevant, ex vivo splenic DC isolated from young (8 wk) and aged (26 mo) C57Bl/6 mice. Splenic DC isolated from aged mice had reduced frequency of plasmacytoid DC (CD11 lowPDCA-1 +) and CD11c +CD8 + DC, and an increase in CD11c +CD8 − DC. Plasmacytoid DC from aged mice had similar IFNα production upon CpG stimulation compared to young mice, and the ability of splenic DC to stimulate T cells was not affected by age. In contrast, aged splenic DC had markedly decreased production of TNFα upon LPS stimulation. Reduced splenic DC activation in aged mice was not due to altered TLR4 expression, but was associated with reduced phosphorylation of STAT1 and STAT3 proteins. Taken together, our results suggested that aging was associated with dysregulation in splenic DC activation and subset differentiation, and may represent one of the factors contributing to the decline in immune function with age.