Aging is associated with a numerical and functional decline in plasmacytoid dendritic cells, whereas myeloid dendritic cells are relatively unaltered in human peripheral blood

Abstract

Dendritic cells (DC) are potent antigen-presenting cells that initiate and regulate T-cell responses. In this study, the numbers and functional cytokine secretions of plasmacytoid and myeloid DC (pDC and mDC, respectively) in peripheral blood from young and elderly subjects were compared. Overall, pDC numbers in peripheral blood were lower in healthy elderly compared with healthy young subjects (p = 0.016). In response to influenza virus stimulation, isolated pDC from healthy elderly subjects secreted less interferon (IFN)–α compared with those from healthy young subjects. The decline in IFN-α secretion was associated with a reduced proportion of pDC that expressed Toll-like receptor–7 or Toll-like receptor-9. In contrast, there was little difference in the numbers and cytokine secretion function between healthy young and healthy elderly subjects (p = 0.82). However, in peripheral blood from frail elderly subjects, the numbers of mDC were severely depleted as compared with either healthy young or elderly subjects (p = 0.014 and 0.007, respectively). Thus, aging was associated with the numerical and functional decline in pDC, but not mDC, in healthy young versus elderly subject group comparisons, while declining health in the elderly can profoundly impact mDC negatively. Because of the importance of pDC for antiviral responses, the age-related changes in pDC likely contribute to the impaired immune response to viral infections in elderly persons, especially when combined with the mDC dysfunction occurring in those with compromised health.

Impaired secretion of interferons by dendritic cells from aged subjects to influenza

“…They produce copious amounts of IFN-I very early in the infection. We (Sridharan et al 2010) and others (Canaday et al 2010;Jing et al 2009;Shodell and Siegal 2002;Stout-Delgado et al 2008;Qian et al 2011) have reported decreased production of IFNs by pDC population in the aged subjects. In addition to pDC, the myeloid dendritic cells (mDCs) subset is also capable of producing IFNs in response to viral infection.…”

The Influence of Age and Sex on the Cell Counts of Peripheral Blood Leukocyte Subpopulations in Chinese Rhesus Macaques

“…A phenomenon has been reported in children during the first decade of life that their pDCs numbers decline rapidly whereas the numbers of mDCs remain relatively stable (20,21). There are at least three studies demonstrated an age-related decline of pDC (22)(23)(24) but two other studies showed no changes (19,25). Conflicting findings have also been reported with regard to the age-related changes in mDCs.…”

The non-canonical Wnt pathway negatively regulates dendritic cell differentiation by inhibiting the expansion of Flt3+ lymphocyte-primed multipotent precursors

“…[28][29][30] However, the molecular mechanisms responsible for these changes in aged mice have not been thoroughly investigated. Considering that Wnt5a expression was elevated in aged hematopoietic precursors and functioned as an important molecule in the aging of hematopoietic systems 25 , the deficiency in DC development in aged mice may also have been elevated due to the expression of Wnt5a.…”