Differential activation of dendritic cells from aged and young subjects by human DNA

Abstract

Dendritic cells act as the interface between the innate and adaptive immunity to direct either an immunogenic or tolerogenic response. They are involved in maintaining peripheral self‐tolerance through clearance of apoptotic cells. Aging is associated with chronic inflammation and autoimmunity. There is impaired dendritic cell mediated phagocytosis. This can result in accumulation of late apoptotic cells that can lyse and release nuclear self antigens such as DNA. Our objective was to determine whether human dendritic cells react to self DNA and if there is a difference between the aged and young subjects. Our results show that‐ 1) intracellular human DNA can activate human dendritic cells by upregulating costimulatory molecules, CD80 and CD86 and inducing the secretion of IFN‐alpha and IL‐6. 2) dendritic cells from aged are more reactive to human DNA as compared to dendritic cells from young. 3) Co‐culture of dendritic cells from aged subjects (pre‐exposed to DNA) with T cells from young resulted in proliferation in contrast to dendritic cells from young individuals where we observed an inhibition of T cell proliferation. These data suggest that dendritic cells from aged individuals may be impaired in their capacity to maintain peripheral self tolerance. This may contribute to the chronic inflammation and autoimmunity associated with aging. Grant support‐ AG027512 from NIH and Ellison Medical Foundation.