Chronological ageing and photoageing of dendritic cells.

Ageing involves the whole organism, including the immune system. Age-dependent alterations of immune functions are located in both the adaptive and innate parts of the immune system. The most important cell type of the innate immune system are the dendritic cells, because their capacity to induce primary immune responses via professional antigen presentation is crucial for the initiation of the adaptive immune response. Evidence exists that dendritic cells of the systemic immune system, represented by lymph-node and blood-derived dendritic cells, as well as of local immunity, represented by Langerhans cells of the skin, participate in ageing processes. In animal models of older mice, dendritic cells of lymph nodes show degenerative characteristics with decreased adhesion molecule expression, less dendrite formation, and reduced antigen trapping capacity, which together imply disruption of functional activity. In contrast, dendritic cells generated from peripheral blood of elderly people were not impaired in their capacity to induce T-cell responses. Together, these findings indicate that in old individuals in vivo dendritic cells of the systemic immune system are reduced in their functional capacity to stimulate immune responses, whereas in vitro generated dendritic cells are fully functional, and therefore might be used in therapeutic approaches to treat age-associated malfunctions of the immune system. Thus far, only morphological descriptions about age-associated changes of dendritic cells (in particular the Langerhans cells) of the skin exist. In the skin, effects of naturally occurring ageing have to be differentiated from UV-radiation-induced ageing processes. The hallmark of Langerhans cell changes in natural as well as UV-induced skin ageing is their reduction in cell number within the epidermis. In addition, they show an atrophic morphology with less dendrites, and less Birbeck granules. It is assumed that these morphological changes are associated with loss of dendritic cell functions, and that this contributes to age-associated development of skin cancer. Therapeutic strategies against natural and UV-induced skin ageing should include a reduction of these changes of Langerhans cells in order to strengthen the immunological functions of the body's outer surface.