Increased reactivity of dendritic cells from aged subjects to self DNA

A. Agrawal, J. Tay, S. Ton, S. Agrawal, S. Gupta
University of California, Irvine, Irvine, CA

Diminished immune function and chronic inflammation are hallmarks of aging. They are also the major cause of morbidity and mortality associated with increasing age. The underlying causes for the same are not well understood. Here we show the increased reactivity of dendritic cells from aged subjects to self antigens as a potential mechanism contributing to age-associated inflammation. Consistent with this, dendritic cells from aged subjects display increased reactivity to intracellular self DNA by secreting enhanced quantities of type I interferon and IL-6 compared to the young controls. Furthermore, this is accompanied by increased upregulation of costimulatory molecules CD80 and CD86.
Importantly, these self DNA primed DCs from aged subjects are also capable of inducing T cell proliferating which is in contrast to young subjects where we observe an inhibition of T cell proliferation. The intracellular self DNA localized in the cytosol and signaled through NFkB signaling pathway. Further investigations revealed that dendritic cells from aged displayed a higher basal level of NFkB activation as determined phosphorylation and trans-activation of p65 unit of NFkB. This suggests an increased state of activation of DCs from aged verses the young which may be responsible for the increased reactivity of DCs from aged to self DNA and contribute to chronic inflammation.

Keywords: Dendritic cells, Aging, Self DNA, Inflammation