Increased reactivity of dendritic cells from aged subjects to self-antigen, the human DNA.
Diminished immune functions and chronic inflammation are hallmarks of aging. The underlying causes are not well understood. In this investigation, we show an increased reactivity of dendritic cells (DCs) from aged subjects to self-Ags as one of the potential mechanisms contributing to age-associated inflammation. Consistent with this, DCs from aged subjects display increased reactivity to intracellular human DNA, a self-Ag, by secreting enhanced quantities of type I IFN and IL-6 compared with the DCs from young subjects. Furthermore, this is accompanied by an increased up-regulation of costimulatory molecules CD80 and CD86. These DNA-primed DCs from aged subjects enhanced T cell proliferation compared with the young subjects, further substantiating our findings. Investigations of signaling mechanisms revealed that DNA-stimulated DCs from aged subjects displayed a significantly higher level of IFN regulatory factor-3 and NF-kappaB activity compared with their young counterparts. More importantly, DCs from aged subjects displayed a higher level of NF-kappaB activation at the basal level, suggesting an increased state of activation. This activated state of DCs may be responsible for their increased reactivity to self-Ags such as DNA, which in turn contributes to the age-associated chronic inflammation.
Agrawal
Anshu
A
Division of Basic and Clinical Immunology, Department of Medicine, University of California, Irvine, CA 92697, USA. aagrawal@uci.edu
Tay
Jia
J
Ton
Steven
S
Agrawal
Sudhanshu
S
Gupta
Sudhir
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D001324:Autoantigens / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics / Q000276:immunology*; D003600:Cytosol / Q000276:immunology / Q000378:metabolism; D004247:DNA / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D016328:NF-kappa B / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
D001324:Autoantigens; D016328:NF-kappa B; D004247:DNA