Impact of aging on antigen presentation cell function of dendritic cells

Abstract

Older people exhibit increased mortality to infections and cancer as compared to younger people, indicating that aging impairs immunity. Dendritic cells (DCs) are key for bridging the innate and adaptive arms of the immune system by priming antigen specific T cells. Discerning how aging impacts DC function to initiate adaptive immune responses is of great biomedical importance as this could lead to the development of novel therapeutics to enhance immunity with aging. This review details reports indicating that aging impairs the antigen presenting function of DCs but highlights other studies indicating preserved DC function with aging. How aging impacts antigen presentation by DCs is complex and without a clear unifying biological underpinning.

Figure 1. Functional changes with age in different dendritic cell subsets

Downregulation of co-stimulatory molecules and MHC class II are observed in cDCs, CD8α⁺ cDCs and pDCs with aging. Aging decreases the capability of CD8α⁺ cDCs to uptake bacterial components. With aging, pDCs exhibit a defect in IRF7 and PI3K upregulation but increased PD-L1 expression, which can inhibit priming of cDC to activate CD8⁺ T cells. IFN-α production by pDCs following viral infection is reduced in old mice and humans. The investigation of cDCs with aging has yielded mixed results with either decreased or preserved production of proinflammatory cytokines and upregulation of costimulatory molecules noted.