Cells of the myeloid and DC system undergo age-related functional changes reportedly contributing to the pathophysiology of age-related diseases such as lung fibrosis and cancer. Human CD14+ peripheral blood monocytes can differentiate into epidermal/mucosal Langerhans cells (CD207+CD1a+ LCs) and monocyte-derived DCs (CD209+ moDCs) in response to TGF-β1 versus IL-4 signaling, respectively. Additionally Notch signaling promotes TGF- β 1-dependent LC differentiation. These moLCs produce low levels of pro-inflammatory cytokines in comparison to high levels produced by moDCs.
Epidermal and mucosal LC frequencies drop during aging in mouse and human; in turn aging is accompanied by enhanced pro-inflammatory cytokine production. To identify age-related molecular changes underlying altered DC subset differentiation and function, we utilized previously established moLC vs moDC differentiation cultures of purified CD14+ monocytes from young and old human adult blood donors.
Despite moLCs and moDCs can be generated from all four analyzed cohorts (young, old, female, male), donors exhibited substantial inter-individual variations, but also showed certain age-related changes in DC differentiation and activation. To corroborate these findings we additionally initiated corresponding LC vs DC differentiation cultures of murine bone marrow cells obtained from young versus old adult mice. Together our data indicate the existence of both hematopoiesis intrinsic and microenvironmental factors governing tissue DC subset changes during aging.